Transvascular method of treating hypertension

ABSTRACT

An intravascular catheter for peri-vascular and/or peri-urethral tissue ablation includes multiple needles advanced through supported guide tubes which expand around a central axis to engage the interior surface of the wall of the renal artery or other vessel of a human body allowing the injection an ablative fluid for ablating tissue, and/or nerve fibers in the outer layer or deep to the outer layer of the vessel. A method of treating hypertension involves injecting an ablative fluid such as ethanol deep into zones in the wall of the renal artery such that the zones of fluid merge to form a circumferential ablation ring at a depth which ablates sympathetic nerves while minimizing injury to interior layers of the vessel wall.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/266,726 filed on Apr. 30, 2014 which is a continuation-in-partapplication of U.S. patent application Ser. No. 13/752,062 filed on Jan.28, 2013, now U.S. Pat. No. 8,740,849, which is a nonprovisionalapplication of U.S. Prov. App. No. 61/719,906 filed on Oct. 29, 2012,all of the foregoing applications of which are hereby incorporated byreference in their entireties. Any and all applications for which aforeign or domestic priority claim is identified in the Application DataSheet as filed with the present application, are hereby incorporated byreference in their entirety under 37 CFR 1.57.

FIELD OF THE INVENTION

This invention is in the field of methods and devices to achieve tissueand nerve fibers for the treatment of hypertension while minimizingdamage to the interior layers of the vessel wall.

BACKGROUND OF THE INVENTION

Since the 1930s it has been known that injury or ablation of thesympathetic nerves in or near the outer layers of the renal arteries candramatically reduce high blood pressure. As far back as 1952, alcoholhas been used for tissue ablation in animal experiments. SpecificallyRobert M. Berne in “Hemodynamics and Sodium Excretion of DenervatedKidney in Anesthetized and Unanesthetized Dog” Am J Physiol, October1952 171:(1) 148-158, describes painting alcohol on the outside of adog's renal artery to produce denervation.

Because of the similarities of anatomy, for the purposes of thisdisclosure, the term target vessel will refer here to the renal artery,for hypertension or congestive heart failure (CHF) applications and theurethra for BPH and prostate applications.

Recent technology for renal denervation include energy delivery devicesusing radiofrequency or ultrasound energy, such as Simplicity™Medtronic, EnligHTN™ from St. Jude Medical which are RF ablationcatheters and One Shot system from Covidien. There are potential risksusing the current technologies for RF ablation to create sympatheticnerve denervation from interior the renal artery for the treatment ofhypertension or congestive heart failure. The short-term complicationsand the long-term sequelae of applying RF energy from interior the renalartery to the wall of the artery are not well defined. This type ofenergy applied within the renal artery, and with transmural renal arteryinjury, may lead to late restenosis, thrombosis, renal artery spasm,embolization of debris into the renal parenchyma, or other problemsinterior the renal artery. There may also be uneven or incompletesympathetic nerve ablation, particularly if there are anatomicanomalies, or atherosclerotic or fibrotic disease interior the renalartery, such that there is non-homogeneous delivery of RF energy Thiscould lead to treatment failures, or the need for additional anddangerous levels of RF energy to ablate the nerves that run along theadventitial plane of the renal artery. Similar issues may also bepresent with the use of ultrasound.

The Simplicity™ system for RF energy delivery also does not allow forefficient circumferential ablation of the renal sympathetic nervefibers. If circumferential RF energy were applied in a ring segment fromwithin the renal artery (energy applied at intimal surface to killnerves in the outer adventitial layer) this could lead to even higherrisks of renal artery stenosis from the circumferential and transmuralthermal injury to the intima, media and adventitia. Finally, the“burning” of the interior wall of the renal artery using RF ablation canbe extremely painful. The long duration of the RF ablation renaldenervation procedure requires sedation and, at times, extremely highdoses of morphine or other opiates, and anesthesia close to generalanesthesia, to control the severe pain associated with repeated burningof the vessel wall. Thus, there are numerous and substantial limitationsof the current approach using RF-based renal sympathetic denervation.Similar limitations apply to ultrasound or other energy deliverytechniques.

The Bullfrog® micro infusion catheter described by Seward et at in U.S.Pat. Nos. 6,547,803 and 7,666,163, which uses an inflatable elasticballoon to expand a single needle against the wall of a blood vessel,could be used for the injection of a chemical ablative solution such asalcohol but it would require multiple applications as those patents donot describe or anticipate the circumferential delivery of an ablativesubstance around the entire circumference of the vessel. The greatestnumber of needles shown by Seward is two and the two needle version ofthe Bullfrog® would be hard to miniaturize to fit through a smallguiding catheter to be used in a renal artery. If only one needle isused, controlled and accurate rotation of any device at the end of acatheter is difficult at best and could be risky if the subsequentinjections are not evenly spaced. This device also does not allow for aprecise, controlled and adjustable depth of delivery of a neuroablativeagent. This device also may have physical constraints regarding thelength of the needle that can be used, thus limiting the ability toinject agents to an adequate depth, particularly in diseased renalarteries with thickened intima. Another limitation of the Bullfrog® isthat inflation of a balloon within the renal artery can induce transientrenal ischemia and possibly late vessel stenosis due to balloon injuryof the intima and media of the artery, as well as causing endothelialcell denudation.

Jacobson and Davis in U.S. Pat. No. 6,302,870 describe a catheter formedication injection into the interior wall of a blood vessel. WhileJacobson includes the concept of multiple needles expanding outward,each with a hilt to limit penetration of the needle into the wall of thevessel, his design depends on rotation of the tube having the needle atits distal end to allow it to get into an outward curving shape. Thehilt design shown of a small disk attached a short distance proximal tothe needle distal end has a fixed diameter which will increase the totaldiameter of the device by at least twice the diameter of the hilt sothat if the hilt is large enough in diameter to stop penetration of theneedle, it will significantly add to the diameter of the device. Using ahilt that has a greater diameter than the tube, increases the deviceprofile, and also prevents the needle from being completely retractedback inside the tubular shaft from which it emerges, keeping the needlesexposed and potentially allowing accidental needlestick injuries tooccur. For either the renal denervation or atrial fibrillationapplication, the length of the needed catheter would make control ofsuch rotation difficult. In addition, the hilts, which limitpenetration, are a fixed distance from the distal end of the needles.There is no built in adjustment on penetration depth which may beimportant if one wishes to selectively target a specific layer in avessel or if one needs to penetrate all the way through to the volumepast the adventitia in vessels with different wall thicknesses. Jacobsonalso does not envision use of the injection catheter for denervation.Finally, FIG. 3 of the Jacobson patent shows a sheath over expandableneedles without a guide wire and the sheath has an open distal end whichmakes advancement through the vascular system more difficult. Also,because of the hilts, if the needles were withdrawn completely inside ofthe sheath they could get stuck inside the sheath and be difficult topush out.

As early as 1980, alcohol has been shown to be effective in providingrenal denervation in animal models as published by Kline et al in“Functional re-innervation and development of supersensitivity to NEafter renal denervation in rats”, American Physiological Society1980:0363-6110/80/0000-0000801.25, pp. R353-R358. Kline states that “95%alcohol was applied to the vessels to destroy any remaining nervefibers. Using this technique for renal denervation, we have found renalnorepinephrine concentration to be over 50% depleted (i.e. <10 mg/gtissue) two weeks after the operation.” Again in 1983 in the article“Effect of renal denervation on arterial pressure in rats with aorticnerve transaction” Hypertension, 1983, 5:468-475, Kline again publishesthat a 95% alcohol solution applied during surgery is effective inablating the nerves surrounding the renal artery in rats. Drug deliverycatheters such as that by described by Jacobson which are designed toinject fluids at multiple points into the wall of an artery have existedsince the 1990s.

McGuckin in U.S. Pat. No. 7,087,040 describes a tumor tissue ablationcatheter having three expandable tines for injection of fluid that exita single needle. The tines expand outward to penetrate the tissue. TheMcGuckin device has an open distal end that does not provide protectionfrom inadvertent needle sticks from the sharpened tines. In addition,the McGuckin device depends on the shaped tines to be of sufficientstrength so that they can expand outward and penetrate the tissue. Toachieve such strength, the tines would have to be so large in diameterthat severe extravascular bleeding would often occur when the tineswould be retracted back following fluid injection for a renaldenervation application. There also is no workable penetration limitingmechanism that will reliably set the depth of penetration of the distalopening from the tines with respect to the interior wall of the vessel,nor is there a preset adjustment for such depth. For the application oftreating liver tumors, the continually adjustable depth of tinepenetration may make sense since multiple injections at several depthsmight be needed. However, for renal denervation, the ability toaccurately adjust the depth or have choice of penetration depth whenchoosing the device to be used is important so as to not infuse theablative fluid too shallow and injure the media of the renal artery ortoo deep and thus miss the nerves that are in the adventitial andperi-adventitial layers of the renal artery.

Chan et al. in U.S. Pat. Nos. 7,273,469 and 8,152,758 describe acatheter assembly with a plurality of delivery cannulas, each connectedto a proximal taper wall of an expandable balloon. Furthermore, there isno workable penetration limiting mechanism in Chan that will reliablyset the depth of penetration of the needles with respect to the interiorwall of the vessel. The Chan device includes independent injectionfittings, with one for each needle, which allows each needle to beaccidentally set to different depths. For catheters having a pluralityof needles, with each needle having an injection fitting, theindependent injection fittings will add complexity to the design andmake the catheter body have a larger diameter. Further, in otherembodiments, the Chan device does not place the delivery cannula flushagainst the inside wall of the target vessel. The Chan device depends onthe needle to be of sufficient strength to expand outward and penetratethe tissue. To achieve such strength, the needle would have to be solarge in diameter that severe extravascular bleeding could often occurwhen the needle is retracted back following fluid injection for a renaldenervation application. Thin needles that will not cause blood loss arequite flimsy and may need both lateral and radial support.

Chan's delivery cannulas are fixedly attached to the outside of aballoon which only moves them outwardly. In some embodiments, theballoon of Chan has a cloverleaf design which would be difficult tomanufacture. The balloon may be required to be made from a non-compliantmaterial, which would limit the diameters usable for a single design. Insome embodiments, the Chan device has a cylindrical balloon that wouldobstruct the blood flow in an artery if used for applications like renaldenervation. In addition, many embodiments of the Chan device appear toobstruct a significant portion of the cross sectional area of the vessellumen, which would obstruct much of, if not all of the blood flow andpotentially lead to undesirable ischemia of distal tissue. Obstructingblood flow to the kidneys may be counterproductive for, e.g., renaldenervation therapies for the treatment of hypertension, sincemaintaining adequate blood flow to the kidneys during a procedure, whichin many cases are already somewhat compromised, can be very important.

Although alcohol has historically been shown to be effective as atherapeutic agent for renal denervation and is indicated by the FDA foruse in the ablation of nerves, there is need for an intravascularinjection system specifically designed for the peri-vascularcircumferential ablation of sympathetic nerve fibers in the outer layersaround the renal arteries with adjustable penetration depth toaccommodate variability in vessel wall thicknesses and to account forthe fact that many renal artery nerves are situated at some distanceoutside of the artery's adventitia.

Throughout this specification any of the terms ablative fluid, ablativesolution and/or ablative substance will be used interchangeably toinclude a liquid or a gaseous substance delivered into a volume oftissue in a human body with the intention of damaging, killing orablating nerves or tissue within that volume of tissue. Also throughoutthis specification, the term inside wall or interior surface applied toa blood vessel, vessel wall, artery or arterial wall mean the same thingwhich is the inside surface of the vessel wall inside of which is thevessel lumen. Also the term injection egress is defined as the distalopening in a needle from which a fluid being injected will emerge. Withrespect to the injection needle, either injection egress or distalopening may be used here interchangeably.

The terminology “deep to” a structure is defined as beyond or outside ofthe structure so that “deep to the adventitia” refers to a volume oftissue outside of the adventitia of an artery.

SUMMARY OF THE INVENTION

Fischell et al. in U.S. patent application Ser. Nos. 13/216,495,13/294,439 and 13/342,521 describe several methods of using expandableneedles to deliver ablative fluid into or deep to the wall of a targetvessel. Each of these applications is hereby incorporated by referencein its entirety. There are two types of embodiments of Ser. Nos.13/216,495, 13/294,439 and 13/342,521 applications, those where theneedles alone expand outward without support from any other structureand those with guide tubes that act as guiding elements to support theneedles as they are advanced into the wall of a target vessel. Thelimitation of the needle alone designs are that if small enough needlesare used to avoid blood loss following penetration through the vesselwall, then the needles may be too flimsy to reliably and uniformlyexpand to their desired position. The use of a cord or wire to connectthe needles together in one embodiment helps some in the area. The useof guide tubes as described in the Fischell application Ser. Nos.13/294,439 and 13/342,521 greatly improves this support, but theunsupported guide tubes themselves depend on their own shape to ensurethat they expand uniformly and properly center the distal portion of thecatheter. Without predictable catheter centering and guide tubeexpansion it may be challenging to achieve accurate and reproducibleneedle penetration to a targeted depth.

Another limitation of the non-supported guide tubes is the lack ofradial support or “backup” as the injection needles are advanced throughthe guide tubes. This can result in the guide tubes being pushed awayfrom the interior surface of the vessel wall as the needles areadvanced. If the guide tubes are stiff enough to provide backup then thedistal section of the catheter becomes more rigid and this may limitcatheter deliverability, and may cause trauma to the wall of the vessel.If the guide tubes are fairly flexible then they can be pushed away fromthe wall during needle advancement, and/or be displaced radially suchthat the injection sites are not distributed symmetrically around thecentral axis of the target vessel.

The present application discloses a Peri-vascular Tissue AblationCatheter (PTAC), that is capable of delivering an ablative fluid toproduce circumferential damage in the tissue that is in the outer layeror beyond the outer layer of a vessel of a human body. The tissue andnerve ablation using this technique can be accomplished in a relativelyshort time as compared with RF ablation catheters, and also has theadvantage of using only a disposable catheter, with no additional,externally located, capital equipment. It will also allow the use ofshort acting anesthetic agents like Versed, and lower doses of narcoticsto reduce or eliminate patient discomfort and pain during the procedure.

The primary focus of use of PTAC is in the treatment of hypertension andcongestive heart failure by renal denervation and the treatment of BPHand prostate cancer by tissue ablation of the prostate from a catheterin the urethra.

Unlike the Bullfrog or current RF ablation devices that work with oneor, at most two points of ablation, the presently disclosed device isdesigned to provide peri-vascular fluid injection allowing a moreuniform circumferential injury to the nerves or other “target” tissue,while minimizing injury to the interior layers of the vessel wall. Theterm “circumferential delivery” is defined here as at least three pointsof simultaneous injection of a suitable ablative solution within avessel wall, or circumferential filling of the space outside of theadventitial layer (outer wall) of a blood vessel. Unlike the Jacobsondevice of U.S. Pat. No. 6,302,870, which does describe circumferentialdelivery, the disclosed device does not depend upon rotation of a tubeto create outward movement nor does it have a fixed diameter hilt tolimit penetration. In addition, while the Jacobson patent shows aversion of his device that pulls back within a sheath like tube, thetube has an open end and the claims of the Jacobson patent require anincrease in diameter to accommodate the manifold that allows the fluidflowing in one lumen from the proximal end of the catheter to egressthrough multiple needles. The preferred embodiment of the presentapplication uses a manifold that fits within the lumen of the tube thusgreatly decreasing the diameter of the catheter which enhances deliveryof the catheter to the desired site within the human body.

Specifically, there is a definite need for such a catheter system thatis capable of highly efficient, and reproducible peri-vascular ablationof the sympathetic nerves surrounding the renal artery, or tissue arounda target vessel, and thus improve the control and treatment ofhypertension, etc. The primary improvement of the present disclosure isthe addition of support structures that improve the uniformity andsymmetry of expansion of the guide tubes of the Fischell Ser. No.13/294,439 and Ser. No. 13/342,521 applications. The support structuresof the present application also support the expanded guide tubes in theradial (outward) direction to provide better backup as the needles areadvanced through the guide tubes and into the wall of the target vessel.

This type of system may also have major advantages over other currenttechnologies by allowing highly efficient, and reproducibleperi-vascular circumferential ablation of the muscle fibers andconductive tissue in the wall of the pulmonary veins near or at theirostium into the left atrium of the heart. Such ablation could interruptatrial fibrillation (AF) and other cardiac arrhythmias. The concepts ofthe present application could also be used to ablate prostatic tissueexternal to the prostatic urethra to treat benign prostatic hypertrophy(BPH) or prostate cancer. Other potential applications of this approachmay also become evident from the various teachings of this patent.

Like the earlier Fischell inventions for the treatment of hypertension,the present application discloses a small diameter catheter, whichincludes multiple expandable injector tubes having sharpened injectionneedles at or near their distal ends that are advanced through guidetubes designed to support and guide the needles into and through theinner layers of the target vessel.

-   -   Some embodiments are described herein that improve upon the        Fischell designs of U.S. patent application Ser. No. 13/294,439.        One embodiment uses three or more manually expanded guide tubes        that are advanced through tubular shafts in the distal portion        of the PTAC. Each tubular shaft having a central buttress with a        shape that curves outward from the longitudinal axis of the PTAC        distal portion. The pre-shaped, curved guide tubes will follow        the shaft and advance outward against the interior surface of        the target vessel.    -   An advantageous feature to this design is the support (backup)        provided by the central buttress and by the mass of the central        catheter body that prevents the guide tubes from pushing away        from the interior wall of the target vessel as the injector        tubes with distal needles are advanced through the vessel wall.        Specifically an outward curving central buttress support that is        part of the distal section of the tubular shaft provides the        above mentioned backup or support. In addition to radial support        for the guide tubes, the buttress in conjunction with the        openings in the distal end of the tubular shaft also support the        uniform spacing and lateral stability of the guide tubes.

There is also a significant advantage of this embodiment over theFischell Ser. No. 13/294,439 application as far as the uniformity andpredictability of device centering and the enhanced control of the rateof advancement of the guide tubes to their position engaging theinterior wall of the target vessel.

The embodiments shown here have significant differences and advantagesover the Chan designs of U.S. Pat. Nos. 7,273,469 and 8,152,758 andother catheters known in the art. Specifically the differences andadvantages may include, for example:

-   -   The guide tubes of the present application are, in some        embodiments, self-expanding and move outward against the inside        wall of the target vessel. The guide tubes are movable distally        and proximally with respect to the distal portion of the        catheter. The guide tubes are manually movable and expandable.    -   In some embodiments, the mechanical support for the guide tubes        include central buttresses, obturators and intraluminal        centering mechanisms which provide mechanical support. Unlike        balloons, these mechanical supports allow much better blood        flow, in some embodiments. As such, in some embodiments, the        catheters, and/or mechanical support structures do not have        balloons.    -   The catheter can be moved through the vessel without obstructing        or substantially obstructing the blood flow through the vessel        Some embodiments are designed to obscure only a portion of cross        sectional area interior lumen of the target vessel (e.g., while        the catheter is in a configuration delivering fluid to a lumen        of the target vessel wall (e.g., obscuring less than about 70%,        65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, or less of the        cross-sectional lumen of the target vessel). The target vessel        can have any diameter, but in some embodiments has a diameter of        between about 3 mm and about 10 mm, between about 3 mm and about        7 mm, between about 4 mm and about 6 mm, or about 3 mm, 4 mm, 5        mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, the        target vessel has a location in which the catheter is deployed,        and the cross-sectional area of the lumen of the target vessel        is between about 30 mm² and about 300 mm², between about 30 mm²        and about 150 mm², between about 50 mm² and about 120 mm², or        about 30 mm², about 50 mm², about 80 mm², about 120 mm², about        150 mm², about 200 mm², about 250 mm², or about 300 mm². In some        embodiments, a location within a target vessel having a luminal        cross-section can be defined as a circle having the largest        possible circumference that still is able to fit entirely within        a cross-section of the lumen of the target vessel. A catheter        can have one, two, three, four, or more radially outwardly        extending structures, including mechanical supports, guide        tubes, needles, and the like akin to sectors of the circle        defining a pie chart. The structures can physically occupy, for        example, sectors making up less than about 300°, 285°, 270°,        255°, 240°, 225°, 210°, 195°, 180°, 165°, 150°, 135°, 120°,        105°, 90°, 75°, 60°, 45° or less of the pie chart, leaving the        remaining sectors of the pie chart advantageously unobstructed        for blood to flow therethrough even when the catheter is        deployed in an expanded state. This is in contrast to a balloon        expanded radially in all directions, which could potentially        occupy a sector made up of the entire 360° of the pie chart.    -   In some embodiments, a balloon supports the guide tubes. The        balloon can be a cylindrical balloon, which is simple to        construct as compared to more complex designs of the prior art.        The cylindrical balloon does not, in some embodiments, obstruct        blood flow sufficient to cause ischemia to distal organs and        tissues. It can be a non-compliant balloon to ensure, even in an        expanded state that there is room between the outside of the        balloon and the inside wall of the target vessel for blood to        flow. In some embodiments, the balloon has a maximum expanded        diameter that is no more than about 90%, 85%, 80%, 75%, 70%,        65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, or less of the        inside diameter of the luminal wall of the target vessel. The        target vessel can have any diameter, but in some embodiments has        a diameter of between about 3 mm and about 10 mm, between about        3 mm and about 7 mm, between about 4 mm and about 6 mm, or about        3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm.    -   In some embodiments, there is only a single injection lumen and        only a single control mechanism to advance the injection        needles, which makes it simpler to construct, reduces the        diameter of the catheter, and can be more reliable than the        prior art. The control mechanism ensures uniform depth for the        needles. This is advantageous for configurations having three or        more needles, for example. Other embodiments can include a        plurality of injection lumens and/or control mechanisms.

The distal portion of the guiding catheter used to access the targetvessel (such as the renal artery) is typically not aligned with thelongitudinal axis of that vessel. Since that is the case, the presentlydisclosed device with a manually expanded embodiment using three guidetubes will be advantageous in several different ways. When the threeguide tubes are advanced outward, one will touch the interior wall ofthe target vessel first and as the guide tubes are further advancedoutward, this first touching guide tube will push the body of the PTACaway from the wall toward the center of the vessel until the secondguide tube touches the interior wall of the target vessel. Then bothtouching guide tubes will push the PTAC further toward the center of thevessel until the third guide tube touches the interior wall of thevessel. Because the guide tubes here are not flimsy structures, and haveeach the same diameter of expansion from the longitudinal axis of thePTAC, this will reproducibly place the distal portion of the PTAC closeto the true center of the vessel. Fluoroscopic imaging of the radiopaquemarkers on the distal portion of the guide tubes provides visualconfirmation of the correct centering of the guide tubes. This centeringcan also be confirmed by using contrast injected from the guidingcatheter, after guide tube deployment.

Another key advantage of this system is the stabilization and “backup”support of the guide tubes as the injector tubes with distal injectionneedles are deployed/advanced through the target vessel wall. The guidetubes, which are now engaged against the interior wall of the targetvessel, are supported by the tubular shafts in the body of the PTAC.Because of this central catheter “backup,” the guide tubes should remainin place as the injection needles penetrate the interior wall of thetarget vessel and advance distally to their preset depth of penetration.The ablative fluid can then be delivered, the needles retracted backinto the guide tubes and the guide tubes and needles retracted back intothe tubular shafts within the distal portion of the PTAC.

A second embodiment that improves upon the teachings of the Fischellapplication Ser. No. 13/294,439 utilizing a self-expanding design,utilizes guide tubes attached to an intraluminal centering mechanism(ICM). One embodiment of the ICM is an expandable wire basket likestructure that opens up against the interior wall of the target vesseland improves the centering, uniform and symmetric expansion, and radialsupport (backup) for the guide tubes to prevent the guide tubes frompulling away from the interior wall of the target vessel as theinjection needles are advanced though that wall. The ICM is particularlyof value if the guide tubes with ICM are self-expanding. The ICM canalso provide additional stability and backup for manually expandableguide tubes such as described in the first embodiment above. The ICM mayinclude specific radiopaque markers to provide visualization duringfluoroscopy of the state of expansion of the ICM. The ICM may alsocreate a minimal degree of offset from the tip of the guide tubes to thevessel interior wall, in order to decrease trauma to the interior layerof the vessel wall by the guide tube tips.

In either embodiment of the presently disclosed PTAC, ablative fluid canbe injected through the distal ends of the injection needles that have adistal opening (injection egress) at or near their distal ends. There isa penetration limiting mechanism as part of the PTAC so that the needleswill only penetrate into or beyond the interior wall of the targetvessel to a preset distance. The preferred embodiment of the penetrationlimiting mechanism is integrated into the proximal portion of the PTACand may include penetration depth adjustment means. The adjustment couldinclude markings that allow for precise depth adjustments.

Adjustment of the penetration depth by mechanisms in the proximal end ofthe PTAC may be either physician controlled or they could be presetduring device production. In the first case, use of intravascularultrasound or other imaging techniques could be used to identify thethickness of the renal artery at the desired site for PVRD. Theclinician would then adjust the depth accordingly. It is also envisionedthat the PTAC could be preset in the factory using the depth adjustmentwhich would not be accessible to the clinician and if multiple depthsare needed, different product codes would be provided that allow fordifferent depths of penetration. For example, three depths might beavailable such as at least 2 mm, at least 3 mm and at least 4 mm.Another advantage of factory adjustable depth is to simplify calibrationand quality production as the variation for each produced PTAC mayrequire a final in factory adjustment of needle depth so that precisedepth of penetration is provided. It is also an advantage for regulatoryfilings that a preset depth or depths be used during trials and forapproval to limit potential error in setting the wrong depth. Finally,it is envisioned that both an internal adjustment for factory productionand calibration and an externally available adjustment with depthmarkings could be integrated into the PTAC.

The adjustment means can be used with the presently disclosed PTAC inone of the following ways:

-   -   1. For adjustment and calibration of a preset penetration depth        during device manufacturing. In this case, the device might be        manufactured with several labeled calibrated preset depths.    -   2. For adjustment of the depth of penetration by the device        operator before or during use of the PTAC. This design would        include markings on the PTAC that show where the depth where the        ablative fluid would be injected. This design is of particular        use for BPH and prostate cancer applications where injections at        a series of different depths would be desirable to allow        delivery into the appropriate volume of prostate tissue.

Ideally, the injection needles should be sufficiently small so thatthere will be virtually no blood loss following the withdrawal of theinjector tubes from the vessel wall. A major advantage of theembodiments disclosed in the present application over the embodimentstaught in the Fischell Ser. No. 13/216,495 application and the JacobsonU.S. Pat. No. 6,302,870 patent is that with such small (<25 gauge)needles, self-expanding structures can be quite flimsy and not reliableto ensure accurate penetration of the vessel wall if not supported bystructures like the presently disclosed guide tubes. The presentlydisclosed guide tubes with attached ICM offer additional advantages overthe unsupported guide tubes of prior Fischell designs as described inthe Ser. Nos. 13/294,439 and 13/342,521 applications. Another advantagebeing the reliable centering of the guide tubes in the vessel andreduced trauma where the expanded mechanism touches the interior of thevessel wall.

There are several different embodiments of the presently disclosed ICMsupported guide tubes. These include:

-   -   1. An expandable structure with proximal, central and distal        portions, constructed from a single tube of a memory metal such        as nitinol or a spring metal. The proximal portion of the        structure would be a guide tube similar to that of Fischell Ser.        No. 13/294,439 and Ser. No. 13/342,521 applications which would        provide a guide for the injector tubes with distal injection        needles. The central and distal portions being the ICM. The        central portion of the structure would have a radiopaque marker        and be designed to open up to touch the interior wall of the        vessel with minimal trauma. The expandable distal portion of the        structure would support the guide tubes and central portion of        the expandable structure facilitating reproducible expansion. A        preferred embodiment of this structure provides a distal        structure with enhanced flexibility. The structure here can be        self-expanding or provide expansion through manipulation of an        Expansion Control Mechanism (ECM) at the proximal end of the        PTAC, or both where the PTAC has a self-expanding ICM and an ECM        that can be used to adjust or enhance the expansion.    -   2. An expandable structure with proximal, central and distal        portions, with a plastic guide tube having an integrated spring        member, the spring member extending distally from the distal end        of the guide tube to form the ICM. The guide tube like those of        the Fischell Ser. No. 13/294,439 and Ser. No. 13/342,521        applications providing a guide for the injector tubes with        distal injection needles. The central portion of the structure        would have a radiopaque marker and be designed to open up to        touch the interior wall of the vessel with minimal trauma. The        expandable distal portion of the structure would support the        guide tubes and central portion of the expandable structure        facilitating reproducible expansion. The structure here can be        self-expanding or provide expansion through manipulation of an        Expansion Control Mechanism (ECM) at the proximal end of the        PTAC, or both where the PTAC has a self-expanding ICM and an ECM        that can be used to adjust or enhance the expansion.    -   3. Expandable guide tubes like those of the Fischell Ser. No.        13/294,439 and Ser. No. 13/342,521 applications providing a        guide for the injector tubes with distal injection needles. The        guide tubes attached to an ICM formed by an expandable balloon,        inflated through a lumen in the shaft of the PTAC.

The injector tubes with distal injection needles of the presentlydisclosed embodiments would typically have a preset curved shape with aradius of curvature similar to that of the guide tubes. Thus as theinjector tubes are advanced through the guide tubes they will follow theguide tube curve and not cause the guide tubes to change position withrespect to the interior wall of the target vessel. The radius ofcurvature of the distal portion of the guide tubes and the distalportion of the injector tubes should be within plus or minus 25% of eachother and ideally within plus or minus 10%.

The embodiments of the present application will function in vessels ofdifferent diameters as the expanded shape of the guide tubes will be setso that, without the constraint of the interior wall of the vessel, theywould achieve an expanded diameter slightly larger than the biggestvessel diameter envisioned for device use. It is also a feature of theembodiments of the present application that the injector tubes curvebackward in the proximal direction as they extend from the distal end ofthe guide tubes and penetrate through the vessel wall.

Because precise depth penetration is preferred, the tubing used for anyof the PTAC proximal or distal sections should have limitedstretchability so they do not elongate during deployment through aguiding catheter into the renal artery. For example, stainless steel,L605 or nitinol hypotubes could be the best material for the proximaltubular sections of the PTAC. Alternately, metal reinforced tubing orhigh durometer plastic with reduced elongation tendencies could be used.Such tubing would also be suitable for the distal section of the PTACwhere more flexibility is needed to go around the nearly right anglebend in the guiding catheter as it enters the renal artery from theaorta.

The injector tubes with distal needles are in fluid communication withan injection lumen in the catheter body, which is in fluid communicationwith an injection port at the proximal end of the PTAC. Such aninjection port would typically include a standard connector such as aLuer connector used to connect to a source of ablative fluid. Alsoenvisioned and described herein is the use of a customized (proximal)fitting (different from a Luer fitting) for the injection port that canimprove safety by disallowing the accidental injection of fluid from astandard syringe, and also to minimize dead space within the catheterwhen injecting ablative agents.

This injection system also anticipates the use of very small gaugeneedles (smaller than 25 gauge) to penetrate the arterial wall, suchthat the needle penetration could be safe, even if targeted to a volumeof tissue that is or beyond the adventitial layer of the aorta, apulmonary vein or renal artery, or prostatic urethra. It is alsoanticipated that the distal needle could be a cutting needle or a coringneedle and with a cutting needle the injection egress/distal openingports could be small injection holes (pores) cut into the sides of theinjector tubes or distal needle, proximal to the cutting needle tip.There should be at least 2 injector tubes but 3 to 8 tubes may be moreappropriate, depending on the diameter of the vessel to be treated andthe ability of the injected ablative fluid to spread within theperi-vascular space. For example, in a 5 mm diameter renal artery, only3 or 4 needles may be needed while in an 8 mm diameter renal, one mightneed 5 to 6 needles.

The preferred embodiment of the present disclosure would use ethanol asthe ablative fluid because this fluid is agrophobic, lipophilic, andspreads quickly in the peri-vascular space. Therefore, only 3 needlesare needed to create circumferential delivery of this ablative agent,which allows one to use a smaller diameter device. It is also envisionedthat use of ethanol or another alcohol plus another neurotoxic agentcould also enhance the spread of the ablative agent in the peri-vascularspace.

A self-expanding embodiment of the presently disclosed PTAC wouldtypically include a tubular, thin-walled sheath that constrains theguide tubes and ICM prior to deployment, during transition from treatingone renal artery to the other, and during removal from the body. Thesheath also allows the distal end of the PTAC to be easily inserted intothe proximal end of a guiding catheter or introducer sheath. The sheathalso serves to protect the operator(s) from possible needle sticks andexposure to blood borne pathogens at the end of the procedure when thePTAC is removed from the patient's body. The sheath would typicallyinclude a radiopaque marker near its distal end to allow the operator toknow its position under fluoroscopy.

The entire PTAC is designed to include a fixed distal guide wire or beadvanced over a guide wire in either an over-the-wire configurationwhere the guide wire lumen runs the entire length of the PTAC or a rapidexchange configuration where the guide wire exits the catheter body atleast 10 cm proximal to the distal end of the PTAC and runs outside ofthe catheter shaft for its proximal section. It is also envisioned thatone could use a soft and tapered distal tip, even without a distalguidewire, for some applications.

The fixed wire version, or the version with the soft tapered distal tipwithout a guidewire are the preferred embodiments, as they would havethe smallest distal diameter. Just proximal to the fixed wire is atapered distal portion of the PTAC which can be called an obturator. Theobturator serves several purposes in the design of the PTAC.

-   -   1. It provides a tapered flexible member that expands in        diameter from the thin fixed distal guide wire to allow the PTAC        to better track around bends such as the bend in the guiding        catheter from the aorta into and through the ostium of the renal        artery.    -   2. The proximal portion of the obturator mates with the sheath        described above to completely surround and constrain the        expandable portions of the PTAC system including guide tubes and        ICM with injection needles.    -   3. The obturator would typically include a radiopaque marker        that would allow the operator to visualize the position of the        obturator as well as its position with respect to the sheath.    -   4. It is envisioned that the obturator could be tapered and soft        such that even without a fixed distal guidewire the advancement        of the device could be safely performed for certain        applications, including in renal denervation.

Fluoroscopic visualization of the correct deployment of the guide tubesand injection needles are highly desirable. There are several ways thatthis goal could be accomplished. It is envisioned that the injectionneedles, guiding tubes and injection tubes could be formed from aradiopaque material such as tantalum or tungsten or coated, or markedwith a radiopaque material such as gold or platinum so as to make themclearly visible using fluoroscopy. The preferred method however is toplace radiopaque marker bands near the distal ends of each guide tubeand include a radiopaque wire within the lumen of each injector tube. Inaddition to providing better visibility, the radiopaque wire in thelumen of each injector tube reduces the internal volume or dead spacewithin the injector tube thereby reducing the amount of fluid needed toflush the internal volume of the PTAC.

It is also envisioned that one or more of the injector needles could beelectrically connected to the proximal end of the PTAC so as to also actas a diagnostic electrode(s) for evaluation of the electrical activityin the area of the vessel wall.

It is also envisioned that one could attach two or more of theexpandable legs to an electrical or RF source to deliver electriccurrent or RF energy to perform tissue and/or nerve ablation.

It is also envisioned that this device could utilize one, or more thanone neuroablative substances to be injected simultaneously, or in asequence of injections, in order to optimize permanent sympathetic nervedisruption in a segment of the renal artery (neurotmesis). Theanticipated neurotoxic agents that could be utilized includes but is notlimited to ethanol, phenol, glycerol, local anesthetics in relativelyhigh concentration (e.g., lidocaine, or other agents such asbupivacaine, tetracaine, benzocaine, etc.), anti-arrhythmic drugs thathave neurotoxicity, botulinum toxin, digoxin or other cardiacglycosides, guanethidine, heated fluids including heated saline,hypertonic saline, hypotonic fluids, KCl or heated neuroablativesubstances such as those listed above.

It is also envisioned that the ablative substance can be hypertonicfluids such as hypertonic saline (extra salt) or hypotonic fluids suchas distilled water. These will cause permanent damage to the nerves andcould be equally as good as alcohol or specific neurotoxins. These canalso be injected hot or cold or at room temperature. The use ofdistilled water, hypotonic saline or hypertonic saline with an injectionvolume of less than 1 ml eliminates one step in the use of the PTACbecause small volumes of these fluids should not be harmful to thekidney and so the need to completely flush the ablative fluid from thePTAC with normal saline to prevent any of the ablative fluid gettinginto the renal artery during catheter withdrawal is no longer needed.This means there would be only one fluid injection step per arteryinstead of two if a more toxic ablative fluid is used.

It is also envisioned that the PTAC catheter could be connected to aheated fluid or steam source to deliver high temperature fluids toablate or injure the target tissue or nerves. The heated fluid could benormal saline, hypertonic fluid, hypotonic fluid alcohol, phenol,lidocaine, or some other combination of fluids. Injection of hot orvaporized normal saline, hypertonic saline, hypotonic saline, ethanol,distilled water or other fluids via the needles could also be performedin order to achieve thermal ablation of target tissue or nerves at andaround the needle injection sites.

The present disclosure also envisions use of anesthetic agents such aslidocaine which if injected first or in or together with an ablativesolution can reduce or eliminate any pain associated with thedenervation procedure.

It is also envisioned that one could utilize imaging techniques such asmultislice CT scan, MRI, intravascular ultrasound (IVUS) or opticalcoherence tomography (OCT) imaging to get an exact measurement of thethickness and anatomy of the target vessel wall (e.g., the renal artery)such that one could know and set the exact and correct penetration depthfor the injection of the ablative agent prior to the advancement of theinjector needles or injector tubes. The use of IVUS prior to use of thePTAC may be particularly useful in order to target the exact depthintended for injection. This exact depth can then be targeted using theadjustable depth of penetration feature or by selection of anappropriate PTAC having a preset depth for the delivery of the ablativefluid. In production, different product codes would be made availablewith package labeling according to the penetration depth.

For use in renal sympathetic nerve ablation, the present preferredmanually expandable (“push”) guide tube embodiment of the PTAC would beused with the following steps (although not every step is essential andsteps may be simplified or modified as will be appreciated by those ofskill in the art):

-   -   1. Sedate the patient using standard techniques for cardiac        catheterization or septal ablation, for example—in a manner        similar to an alcohol septal ablation, (Versed and narcotic        analgesic).    -   2. Engage a first renal artery with a guiding catheter placed        through the femoral or radial artery using standard arterial        access methods.    -   3. After flushing all lumens of the PTAC, including the        injection lumen, with saline, advance the distal end of the PTAC        with a fixed distal guidewire position into the guiding        catheter. Advance the distal portion of the PTAC through and        beyond the distal end of the guiding catheter, until the        radiopaque marker on the obturator or guide tubes are at the        desired location in the renal artery.    -   4. Manually advance the guide tubes out of their tubular shafts        using the mechanism in the proximal section of the PTAC until        they are fully expanded against the interior wall of the target        vessel. Expansion can be confirmed by visualization of the        radiopaque tips of the guide tubes.    -   5. Next, the injection tubes/needles are advanced coaxially        through the guide tubes to penetrate through the internal        elastic lamina (IEL) and media of the artery, then through the        external elastic lamina (EEL) to a preset distance (typically        between 0.5 to 4 mm but preferably about 2-4 mm) beyond the IEL        into the outer (adventitial and/or peri-adventitial) layer(s) of        the vessel wall of the renal artery. The injection tubes/needles        are thereby positioned to deliver the neuroablative agent(s) at        or “deep to” (outside of) the adventitial plane. The depth of        2-4 mm deep relative to the IEL will minimize intimal and medial        renal artery injury. The normal thickness of the media in a        renal artery is between 0.5 and 0.8 mm. The depth limitation        feature of the embodiments disclosed in the present disclosure        has the distal opening of the needles set to be a fixed distance        beyond the distal end of the guide tubes. In a normal renal        artery the guide tubes would be positioned against the IEL which        is normally situated at or near the interior wall of the target        vessel. If there is intimal thickening from plaque or neointimal        hyperplasia within the artery as seen by angiography, IVUS or        OCT, then as much as 3-6 mm of penetration depth beyond the end        of the end of the guide tube may be needed. Specific product        codes (e.g., preset designs) with preset greater penetration        depths or user available adjustments in the handle of the PTAC        are envisioned to facilitate this. If the vessel has a stenosis,        it would be preferable to pick the site for needle penetration        away from the stenosis and to treat the stenosis as needed with        Percutaneous Coronary Intervention (PCI).    -   6. Inject an appropriate volume of the ablative agent which can        be an ablative fluid, such as ethanol (ethyl alcohol), distilled        water, hypertonic saline, hypotonic saline, phenol, glycerol,        lidocaine, bupivacaine, tetracaine, benzocaine, guanethidine,        botulinum toxin, glycosides or any other appropriate neurotoxic        fluid. This could include a combination of 2 or more        neuroablative fluids or local anesthetic agents together or in        sequence (local anesthetic first to diminish discomfort,        followed by delivery of the ablative agent) and/or high        temperature fluids (or steam), or extremely cold (cryoablative)        fluid into the vessel wall and/or the volume just outside of the        vessel. A typical injection would be 0.1-3.0 ml. This should        produce a multiplicity of ablation zones (one for each injector        tube/needle) that will intersect to form an ablative ring around        the circumference of the target vessel. Contrast could be added        to the injection either during a test injection before the        neuroablative agent or during the therapeutic injection to allow        x-ray visualization of the ablation zone. With ethanol, as an        ablative agent, a volume of less than 0.5 ml is sufficient for        this infusion as it will not only completely fill the needed        volume including the sympathetic nerves, but is small enough        that if accidentally discharged into the renal artery, would not        harm the patient's kidneys. Ideally, a volume of 0.1 ml to 0.3        ml of ethanol should be used.    -   7. Inject normal saline solution into the PTAC sufficient to        completely flush the ablative agent out of the injection        lumen(s) (dead space) of the PTAC including the injector tubes        with distal injection needles. This prevents any of the ablative        agent from accidentally getting into the renal artery during the        withdrawal of the needles into the PTAC. Such accidental        discharge into the renal artery could cause damage to the        kidneys. This step may be avoided if distilled water, hypotonic        or hypertonic saline is used as the ablative agent or if the        volume of ablative agent is small enough such that the potential        for kidney damage by accidental discharge into the renal artery        is reduced. It is also envisioned that with ethanol, where less        than 0.5 ml is needed for ablation, that flushing may be        unnecessary as 0.5 ml in the presence of normal blood flow will        not harm the kidneys.    -   8. Retract the PTAC injector tubes/needles back inside the guide        tubes.    -   9. Retract the guide tubes back into the tubular shafts of the        PTAC.    -   10. In some cases, one could rotate the PTAC 30-90 degrees, or        relocate the PTAC 0.2 to 4 cm distal or proximal to the first        injection site and then repeat the injection if needed to make a        second ring of tissue damage to create even greater        denervation/nerve ablation.    -   11. The same methods as per prior steps can be repeated to        ablate tissue in the opposite (contra-lateral) renal artery.    -   12. Remove the PTAC from the guiding catheter completely.    -   13. Remove all remaining apparatus from the body.

A simplified version of the prior procedure avoids the use of salineflushes for the catheter injection lumen/dead space as follows:

-   -   1. Sedate the patient using standard techniques for cardiac        catheterization or septal ablation, for example—in a manner        similar to an alcohol septal ablation, (Versed and narcotic        analgesic).    -   2. Engage a first renal artery with a guiding catheter placed        through the femoral or radial artery using standard arterial        access methods with the distal end of the guiding catheter being        situated beyond the ostium of the renal artery.    -   3. Outside of the body, with the needle guiding elements/guide        tubes and needles fully expanded, flush the injection lumen with        the ablative fluid.    -   4. Outside of the body, flush all lumens of the PTAC except the        injection lumen with saline. With enough saline flowing through        the guide tubes and catheter distal openings, this should wash        any residual ablative fluid off of the outer surfaces of the        PTAC.    -   5. Retract the needles and needle guiding elements/guide tubes.    -   6. Advance the PTAC through the guiding catheter to the desired        spot in the renal artery.    -   7. Manually advance the needle guiding elements/guide tubes    -   8. Next, advance the injection tubes/needles to penetrate        through the internal elastic lamina (IEL) to the desired depth.    -   9. Inject an appropriate volume of the ablative agent/fluid.    -   10. Retract the PTAC injector tubes/needles back inside the        guide tubes.    -   11. Retract the guide tubes back into the tubular shafts of the        PTAC.    -   12. Retract the PTAC back into the guiding catheter.    -   13. If desired, move the guiding catheter to the opposite        (contra-lateral) renal artery.    -   14. Repeat steps 6 through 11.    -   15. Remove the PTAC from the guiding catheter completely.    -   16. Remove all remaining apparatus from the body.

This simplified procedure should be safe because the amount of ablativefluid that can leak out of the refracted injection needles issignificantly less than the dead space in the PTAC. Specifically, whileas much as 0.5 ml of many ablative fluids such as ethanol can be safelyinjected into the renal artery without causing kidney damage, even ifthe entire internal volume were to leak out into the renal artery,because the dead space is less than 0.3 ml, it would not harm thekidney. In the real world, less than 10% of the internal volume (e.g.,less than 0.03 ml) can ever leak out of the closed PTAC so thesimplified procedure above should be extremely safe.

For use in renal sympathetic nerve ablation, the embodiment of thepresently disclosed PTAC with ICM would be used with the following steps(although not every step is essential and steps may be simplified ormodified as will be appreciated by those of skill in the art):

-   -   1. Sedate the patient using standard techniques for cardiac        catheterization or septal ablation, for example—in a manner        similar to an alcohol septal ablation, (Versed and narcotic        analgesic).    -   2. Engage a first renal artery with a guiding catheter placed        through the femoral or radial artery using standard arterial        access methods.    -   3. After flushing all lumens of the PTAC, including the        injection lumen, with saline, advance the distal end of the PTAC        in its closed position into the guiding catheter. Advance the        distal portion of the PTAC through and beyond the distal end of        the guiding catheter, until the radiopaque marker on the ICM or        guide tubes are at the desired location in the renal artery.    -   4. Pull back the sheath allowing the expandable guide tubes with        ICM to open up against the interior wall of the renal artery. If        the ICM is self-expanding this will happen automatically, if the        expansion is controlled by a proximal expansion control        mechanism (ECM), then the ECM can be manipulated by the operator        to cause expansion of the ICM and guide tubes. Expansions can be        confirmed by visualization of the radiopaque tips of the guide        tubes and/or the radiopaque markers on the ICM.    -   5. Next, the injection tubes/needles are advanced coaxially        through the guide tubes to penetrate through the internal        elastic lamina (IEL) at a preset distance (typically between 0.5        to 4 mm but preferably about 2-4 mm) beyond the IEL into the        outer (adventitial and/or peri-adventitial) layer(s) of the        vessel wall of the renal artery to deliver the neuroablative        agent(s) at or deep to the adventitial plane. The depth of 2-4        mm deep relative to the IEL will minimize intimal and medial        renal artery injury.    -   6. Inject an appropriate volume of the ablative agent which can        be an ablative fluid, such as ethanol (ethyl alcohol), distilled        water, hypertonic saline, hypotonic saline, phenol, glycerol,        lidocaine, bupivacaine, tetracaine, benzocaine, guanethidine,        botulinum toxin, glycosides or other appropriate neurotoxic        fluid. This could include a combination of 2 or more        neuroablative fluids or local anesthetic agents together or in        sequence (local anesthetic first to diminish discomfort,        followed by delivery of the ablative agent) and/or high        temperature fluids (or steam), or extremely cold (cryoablative)        fluid into the vessel wall and/or the volume just outside of the        vessel. A typical injection would be 0.1-5 ml. This should        produce a multiplicity of ablation zones (one for each injector        tube/needles) that will intersect to form an ablative ring        around the circumference of the target vessel. Contrast could be        added to the injection either during a test injection before the        neuroablative agent or during the therapeutic injection to allow        x-ray visualization of the ablation zone. With ethanol, as an        ablative agent, a volume of less than 0.5 ml is sufficient for        this infusion as it will not only completely fill the needed        volume including the sympathetic nerves, but is small enough        that if accidentally discharged into the renal artery, would not        harm the patient's kidneys. Ideally, a volume of 0.1 ml to 0.3        ml of ethanol should be used.    -   7. Inject normal saline solution into the PTAC sufficient to        completely flush the ablative agent out of the injection        lumen(s) (dead space) of the PTAC including the injector tubes        with distal injection needles. This prevents any of the ablative        agent from accidentally getting into the renal artery during        pull back of the needles into the PTAC. Such accidental        discharge into the renal artery could cause damage to the        kidneys. This step may be avoided if distilled water, hypotonic        or hypertonic saline is used as the ablative agent or the volume        of ablative agent is small enough that the potential for kidney        damage by accidental discharge into the renal artery is reduced.    -   8. Retract the PTAC injector tubes/needles back inside the guide        tubes. Then, retract and re-sheath the guide tubes with ICM back        under the sheath completely surrounding the sharpened needles.        The entire PTAC can then be pulled back into the guiding        catheter.    -   9. In some cases, one could rotate the PTAC 30-90 degrees, or        relocate the PTAC 0.2 to 4 cm distal or proximal to the first        injection site and then repeat the injection if needed to make a        second ring of tissue damage to create even greater        denervation/nerve ablation.    -   10. The same methods as per prior steps can be repeated to        ablate tissue in the contra-lateral renal artery.    -   11. Remove the PTAC from the guiding catheter completely.    -   12. Remove all remaining apparatus from the body.

In both embodiments of the present application, as described in themethods above, the means to limit needle penetration of the vessel wallis included in the proximal portion of the PTAC. A handle or handles areenvisioned that would be used by the operator to cause first theexpansion of the guide tubes and second the advancement of the injectionneedles. The reverse motion of these mechanisms would then retract theneedles back into the guide tubes and then retract the guide tubes backinto the catheter body or under a sheath. Fischell et al in U.S. patentapplication Ser. Nos. 13/643,070, 13/643,066 and 13/643,065 describessuch control mechanisms for advancing and retracting distal structuressuch as sheaths, guide tubes and injector tubes with distal injectionneedles. Interlocks and locking mechanisms to prevent accidentalmovement out of sequence of these mechanisms are also described.

Similarly, Fischell et al describes the proximal section with ports forflushing and ablative fluid injection. The embodiments disclosed in thepresent application would have similar structures and controls in theproximal section. The mid-section of the catheter would typically bethree concentric tubes. In the manually expandable embodiment withtubular shafts, there is an outer tube that forms the main body of thecatheter. A middle tube controls the advancement and retraction of theguide tubes and an inner tube controls the advancement and retraction ofthe injector tubes with distal injection needles. The lumen of the innertube is also the lumen that carries the ablative fluid injected in theinjection port in the proximal section of the PTAC to the lumens of theinjector tubes and injection needles and finally out though the distalopening at or near the distal ends of the injection needles.

Another important feature of the presently disclosed PTAC is a designthat reduces the internal volume of the PTAC (the “dead space”) tominimize the amount of saline needed to flush the ablative fluid out ofthe catheter into the desired volume of tissue. It is anticipated thatless than 0.5 ml of an ablative fluid such as ethanol will be needed toperform PVRD. The dead space should be less than 0.5 ml and ideally lessthan 0.2 ml. With certain design features it is conceived that the deadspace can be reduced to less than 0.1 ml. Such features include using asmall diameter <0.5 mm ID hypotube for the inner tube used for fluidinjection for the PTAC, including a wire placed into the full length ofthe hypotube/inner tube to reduce the volume of the hypotube and thusreduce the PTAC dead space and/or designing the proximal injection portand or injection manifold at the proximal end of the PTAC to have lowvolume by having small <0.5 mm inner diameter and a short, <2 cm length.

It is an important feature of this invention that the guide tubes areneedle guiding elements for the advance-able, ultra-thin injectionneedles. Specifically, prior art such as Jacobson that describes curvedneedles that are advanced outward from a central catheter to penetratethe interior wall of a target vessel, have bare needles that areadvanced on their own from the distal end or the side of a catheter.Without additional guiding (support) during advancement, needles thatare thin enough to not cause blood loss following withdrawal from thewall of the artery are generally too flimsy to reliably penetrate asdesired into the vessel wall. Thus it is envisioned that a key aspect ofthe embodiments disclosed in the present application is the inclusion ofneedle guiding elements such as guide tubes that allow the ultra-thininjection needles to be reliably advanced into the wall of a targetvessel to the desired depth. Such guiding elements need not be a tube orhave a round cross-section, they could be a half or partial tube, theycan be a structure with a slot that provides a guide for theadvance-able needles, and a guiding structure could be any expandablestructure such as a spring that expands outward and provides radialsupport and a guide for the needles. The terms “expand” and “expands”are intended to refer to motion of a structure from a first positionrelatively closer to a longitudinal axis of the catheter to at least asecond position that is relatively farther away from the longitudinalaxis, whether the motion is by expansion, deflection, pivoting, or othermechanism. It is desirable that the needle guiding elements expandoutward from the central catheter.

What is also unique about the embodiments disclosed in the presentapplication is the use of additional structures to provide radial andlateral support for the needle guiding elements. This is importantbecause one needs a uniform penetration and angular spread of themultiple needles. In addition, as the needles are advanced, and guidedby a “guiding element,” (e.g., the guide tube) the guiding element can,if unsupported, back away from the desired position against the interiorwall of the vessel. For this reason, the present disclosure teaches thedesign of structures that provide radial (“backup”) support for theneedle guiding elements that provide resistance to the guiding elementsbacking away from the interior surface as the needles are advanced intothe wall of the vessel.

Another embodiment of the present disclosure simplifies the constructionby combining the guide tube and injector tube into a single injectortube. This also reduces the steps of operation. Specifically, theinjector needle is permanently attached inside the injector tube whichis advanced and retracted through the tubular shaft. The distal end ofthe injector tube is of larger diameter than the injector needle andprovides the “stop” that limits the penetration of the injector needleinto the wall of the target vessel.

Yet another embodiment of the present disclosure uses an inflatableballoon to expand the guide tubes through which the injector tubes withdistal needles are advanced into the wall of the target vessel. Theballoon may be compliant, semi-compliant or non-compliant. However, anelastic compliant balloon is preferred as it would allow the diameter ofthe outer edges of the expanded guide tubes to be easily set by usingdifferent inflation pressures for the balloon. Attaching the guide tubesto the outside of the balloon simplifies construction as compared withattempting to place guide tubes within the balloon and also allows thedistal end of the guide tubes to be the points of engagement with theinterior wall of the target vessel so that the external surface of theballoon does not touch the wall. Having the balloon touch the wall canremove the endothelial cells and produce neointimal hyperplasia which isundesirable. The balloon expandable embodiment may have the guide tubesand injector tubes combined where the balloon expansion causes theneedles to expand outward to penetrate the wall. The balloon expandableembodiments may also use an optional sheath to enclose the expandabledistal portion to facilitate delivery and reduce the chance ofneedlestick injuries during handling, insertion and removal of thecatheter. Having the guide tubes or injector tubes attached to theoutside of an expandable elastic balloon will also provide radial andlateral stability for the thin needles to ensure both uniform expansionand backup as the needles are advanced through the wall of the targetvessel.

Another feature of the embodiments of the present application is to havethe injection port for injecting the ablative fluid would be anon-standard fitting with a small diameter lumen. In addition, thepresent application envisions matching syringes that would have the matefor the non-standard fitting of the injection port. Such a syringe couldcontain the appropriate volume for injection of fluids into the wall ofthe target vessel including ablative fluids or a saline solution used toflush the injector tubes prior to insertion of the PTAC into the vesselto be treated.

Another feature of the PTAC disclosed in the present application is thatthe flow though the multiple needles should be matched to provide auniform circumferential delivery of the ablative fluid from each of theneedle tips.

Another feature of the PTAC disclosed in the present application givesthe user the ability to lock down the longitudinal motion of thecatheter once the distal portion is at the desired site in the renalartery. There are several ways of doing this that can be accomplishedusing a number of specific features of the PTAC as described herein.These design features include:

-   -   1. Tightening the Tuohy-Borst valve at the proximal end of the        renal guiding catheter to disallow longitudinal motion of the        PTAC.    -   2. Adding an adhesive pad or Velcro to firmly attach a proximal        portion of the PTAC to the skin of the patient or to the        proximal end of the guiding catheter.    -   3. Mechanisms in the proximal section or handle of the PTAC that        lock the PTAC longitudinal motion with respect to the guiding        catheter. These can include:        -   a. A clip that slides coaxially over the outer surface of            the PTAC which can be advanced distally until it clips onto            the outside of proximal end of the guiding catheter. When            clipped onto the guiding catheter, the clip would create a            frictional lock with the shaft of the PTAC.        -   b. A locking tube that runs distally into the proximal            portion of the guiding catheter where the proximal end of            the locking tube attaches to the mechanisms in the proximal            portion/handle of the PTAC that actuate the guide tubes            and/or the injector tubes. Longitudinal or rotational motion            of the locking tube will cause the locking tubes distal            section to engage the proximal portion of the guiding            catheter to prevent longitudinal motion of the PTAC. For            example, the tube diameter could get bigger to cause it to            have a frictional lock with either the Tuohy-Borst at the            proximal end of the guiding catheter or the interior surface            of the guiding catheter itself.

Thus a feature of the presently disclosed PTAC is to have apercutaneously delivered catheter with expandable supported needleguiding elements through which injection needles are advanced forinjection of an ablative fluid into or beyond the outer layers of therenal artery whose design will reduce or prevent the risk of injury tothe intimal and media layers of the renal artery.

Another aspect of the present application is to have a PTAC design withmanually expandable guide tubes/needle guiding elements which areadvanced outward from the body of the PTAC, the PTAC having supportstructures that support the guide tubes/needle guiding elements radiallyagainst the interior wall of the target vessel.

Another aspect of the present disclosure is to have a PTAC design withmanually expandable guide tubes/needle guiding elements which areadvanced outwardly from tubular shafts with distal openings in thedistal portion of the body of the PTAC, the tubular shafts and openingsproviding lateral support for the guide tubes/needle guiding elements toensure they expand uniformly and symmetrically in acircumferential/lateral distribution. For example, if three guidetubes/needle guiding elements are used, the lateral support will help toensure that a ˜120 degree angle is maintained between adjacent guidetubes/needle guiding elements, as the guide tubes/needle guidingelements expand outward.

Another aspect of an embodiment of the PTAC disclosed in the presentapplication is to have an intraluminal centering mechanism (ICM)attached to the guide tubes/needle guiding elements that providesadditional radial support or backup to prevent the guide tubes/needleguiding elements from being pushed away from the interior wall of thetarget vessel as the injector tubes with distal injection needles areadvanced through the guide tubes/needle guiding elements into theperi-vascular space.

Another aspect of the PTAC of the present disclosure is to have anintraluminal centering mechanism (ICM) attached to the guidetubes/needle guiding elements that provides additional lateral supportto enhance the uniformity of guide tube expansion.

Still another aspect of the PTAC of the present application is to havean intraluminal centering mechanism that reduces the potential trauma tothe interior wall of the target vessel from the guide tubes that guidethe penetration of the injector needles for tissue ablation.

Still another aspect of the present disclosure is to have a two stepinjection method for renal denervation where the catheter is filled withnormal saline before insertion into the body; then after needledeployment a first injection of ablative fluid (for example ethanol) isdone, followed by a second step to flush all the ablative fluid out ofthe catheter dead space using normal saline or a similar fluid that isnon-toxic to the kidneys. The PTAC is then closed and the same twoinjection steps are used for the other renal artery.

Still another aspect of the present application is to have a one stepinjection method for renal denervation of each artery, where thecatheter is filled with the ablative fluid before insertion into thebody; then after needle deployment a single injection of ablative fluid(for example ethanol) is done. The PTAC is then closed and the samesingle injection step is used for the other renal artery.

Still another aspect of the present disclosure is to have at least threeguide tubes/needle guiding elements in the PTAC each having a radiopaquemarker. The guide tubes/needle guiding elements being manuallyexpandable outward from within a set of tubular shafts which provideadditional support and backup to stabilize each guide tube/needleguiding element against the interior wall of the target vessel.Expansion of the guide tubes/needle guiding elements is accomplished bymanipulation of a mechanism in the proximal portion of the PTAC.

Still another aspect of the invention is to have curved expandableinjector tubes with injection needles that are able to be coaxiallyadvanced through guide tubes. A distal portion of the injector tubeshaving a radius of curvature that is similar to that of the guide tubes.

Yet another aspect of an embodiment of the present application is tocombine the guide tube and injector tube into an injector tube withthickened proximal portion that acts as the penetration limiter and canbe manufactured to set a specific depth of injection.

Yet another aspect of the PTAC of the present disclosure is to use anexpandable balloon to provide radial expansion and support for the guidetubes/needle guiding elements and/or injector tubes with distalinjection needles.

Yet another aspect of the PTAC of the present application is to have theflow resistance of each of the multiplicity of needles be approximatelythe same.

Yet another aspect of the PTAC of the present disclosure is to includeone or more of the following radiopaque markers to assist inpositioning, opening, closing and using the PTAC. These include thefollowing:

-   -   A radiopaque ring marking the distal end of the sheath;    -   Radiopaque markers at, or very close to the ends of the guide        tubes using either metal bands or plastic with a radiopaque        filler such as barium or tungsten;    -   Radiopaque markers on the distal portion of the injection        needles;    -   Radiopaque wires inside the lumen of the injector tubes and/or        injection needles;    -   The distal fixed guide wire of the PTAC being radiopaque (e.g.,        using platinum wire);    -   Radiopaque markers on the intraluminal centering mechanism        (ICM).

Throughout this specification the terms injector tube with distalinjection needle is used to specify a tube with a sharpened distal endthat penetrates into tissue and is used to inject a fluid into thattissue. Such a structure could also be called a hypodermic needle, aninjection needle or simply a needle. In addition, the terms element andstructure may be used interchangeably within the scope of thisapplication. The term Luer fitting may be used throughout thisapplication to mean a tapered Luer fitting without a screw cap or a LuerLock fitting that has a screw cap.

The present disclosure, in some aspects, provides a catheter for fluiddelivery through at least two injection needles into tissue outside ofthe interior wall of a target vessel of a human body. In someembodiments, the catheter is provided having a central axis extending ina longitudinal direction and a fluid injection lumen. The catheter caninclude at least two guide tubes configured to advance distally andexpand outwardly toward the interior wall of the target vessel. Thecatheter can include a mechanical support structure having a deflectionsurface. The deflection surface deflects the at least two guide tubestoward the interior wall of the target vessel. The catheter can includeat least two injector tubes having distal injection needles. Each distalinjection needle can have an injection lumen in fluid communication withthe fluid injection lumen of the catheter body. The at least twoinjector tubes are configured to advance distally and expand outwardly,guided by the at least two guide tubes to penetrate the interior wall ofthe target vessel. The distal injection needles can have an opening forfluid delivery.

The present disclosure, in some aspects, provides a catheter for fluiddelivery through at least two injection needles into tissue outside ofthe interior wall of a target vessel of a human body. In someembodiment, the catheter is provided having a central axis extending ina longitudinal direction and also comprising a fluid injection lumen.The catheter can include a sheath having a distal closed position and aproximal open position. The catheter can include at least twoself-expanding guide tubes adapted to expand outwardly toward theinterior wall of the target vessel when the sheath is moved from itsdistal closed position to its proximal open position. The catheter canhave a handle located near the proximal end of the catheter. The handlecan be configured to move the sheath in the longitudinal direction withrespect to the self-expanding guide tubes. The catheter can include atleast two injector tubes with distal injection needles each having aninjection lumen in fluid communication with the fluid injection lumen ofthe catheter body. The at least two injector tubes with distal injectionneedles are configured to be advanced outwardly, guided by the at leasttwo guide tubes to penetrate the interior wall of the target vessel. Theat least two injection needles can have a distal opening for fluiddelivery into the tissue outside of the interior wall of the targetvessel. The catheter can include a mechanical support structure. Themechanical support structure can provide support for the at least twoself-expanding guide tubes in a direction selected from the groupconsisting of a) radial, in which the mechanical support structuresupports each guide tube in a radial direction, and b) lateral, in whichthe mechanical support structure supports each guide tube in a lateraldirection. The distal end of the injection needles can be withdrawn intothe at least two self-expanding guide tubes and the at least twoself-expanding guide tubes can be withdrawn into the catheter body inthe distal closed position. The distal closed position can preventneedlestick injuries form the sharpened distal end of the injectionneedles.

The present disclosure, in some aspects, provides a catheter for fluiddelivery through at least three injection needles into tissue outside ofthe interior wall of a target vessel of a human body. In someembodiment, the catheter is provided having a catheter body having acentral axis extending in a longitudinal direction and a fluid injectionlumen. The catheter can include at least three guide tubes adapted toadvance distally and expand outwardly toward the interior wall of thetarget vessel. The catheter can include a handle located near a proximalend of the catheter. The handle can include a plurality of fittings. Thecatheter can include a fluid injection port located near a proximal endof the catheter. The fluid injection port can have a non-standardconnector that is different from any other fitting on the handle of thecatheter and configured to reduce the chance of accidentally injectingthe ablative fluid into any other fitting. The injection port can be influid communication with the fluid injection lumen of the catheter. Thecatheter can include at least three injector tubes each comprisingdistal injection needles. Each of the at least three injector tubes caninclude an injection lumen in fluid communication with the fluidinjection lumen of the catheter body. The at least three injector tubesare configured to be advanced outwardly, guided by the at least threeguide tubes to penetrate the interior wall of the target vessel. Theinjection needles can have a distal opening for fluid delivery into thetissue outside of the interior wall of the target vessel.

The present disclosure, in some aspects, provides a catheter for fluiddelivery through at least two injection needles into tissue outside ofthe interior wall of a target vessel of a human body. The catheterprovided can include a catheter body comprising a central axis extendingin a longitudinal direction and also having a fluid injection lumen. Thecatheter can include at least two guide tubes configured to advancedistally and expand outwardly toward the interior wall of the targetvessel. The catheter can include a mechanical support structureconfigured to support each expanded needle guiding element in adirection selected from the group consisting of a) radial, in which themechanical support structure supports each needle guiding element in aradial direction, and b) lateral, in which the mechanical supportstructure supports each needle guiding element in a lateral direction.The catheter can include at least two injector tubes with distalinjection needles. Each of at least two injector tubes can have aninjection lumen in fluid communication with the fluid injection lumen ofthe catheter body. The at least two injector tubes with distal injectionneedles are configured to be advanced outwardly, guided by the at leasttwo guide tubes to penetrate the interior wall of the target vessel. Theinjection needles can have a distal opening for fluid delivery into thetissue outside of the interior wall of the target vessel. The cathetercan be sized and configured to obscure less than about 50%, 40%, 30%, orless of the cross sectional area of the lumen of the target vessel whenthe catheter is in a configuration penetrating the interior wall of thetarget vessel, for example, when the target vessel has a cross sectionalarea of between about 30 mm² and about 300 mm², between about 30 mm² andabout 150 mm², between about 50 mm² and about 120 mm², or about 30 mm²,about 50 mm², about 80 mm², about 120 mm², about 150 mm², about 200 mm²,about 250 mm², or about 300 mm².

The present disclosure, in some aspects, provides a method for fluiddelivery to an interior wall of a target vessel. The method can includethe step of providing a catheter body. The method can include the stepof providing a mechanical support structure configured to support atleast two guide tubes in a direction selected from the group consistingof a) radial, in which the mechanical support structure supports eachguide tube in a radial direction, and b) lateral, in which themechanical support structure supports each guide tube in a lateraldirection. The method can include the step of advancing distally andexpanding outwardly at least two guide tubes toward the interior wall ofthe target vessel. The method can include the step of deflecting thedistally moving guide tubes outward toward the interior wall of thetarget vessel. The method can include the step of advancing distally andexpanding outwardly at least two injector tubes with distal injectionneedles. The method can include the step of delivering fluid to theinterior wall of the target vessel via the injection needles, whereinwhile delivering fluid the catheter body obstructs less than about 50%,40%, 30%, or less of the cross sectional area of the lumen of the targetvessel. The method can include the step of supporting each guide tuberadially, by the mechanical support structure. The method can includethe step of supporting each guide tube laterally, by the mechanicalsupport structure. The method can include the step of penetrating theinterior wall of the target vessel with the distal injection needles.The method can include the step of delivering fluid through the distalopening of the injection needles. The method can include the step ofcentering the catheter by touching the at least two guide tubes to theinterior wall of the target vessel. The method can include the step ofsimultaneously advancing outward the at least two guide tubes. Themethod can include the step of simultaneously advancing outward the atleast two injector tubes. The method can include the step of penetratingthe tissue outside of the interior wall of the target vessel to an equaldepth.

In some embodiments, the catheter can include a mechanical supportstructure having a deflection surface. The deflection surface deflectsthe guide tubes outward toward the interior wall of the target vessel.In some embodiments, the mechanical support structure is a centralbuttress support located internal to a distal portion of the catheterbody. The central buttress support is adapted to support the two guidetubes. In some embodiments, the catheter can has a lateral supportstructure adapted to support the guide tubes as they expand outward. Thelateral support structure can be, for example, a) a tubular shaftlocated near the distal portion of the catheter body, the tubular shafthaving an opening through which at least one of the two guide tubes isadvanced, b) an intraluminal centering mechanism attached to the twoguide tubes, or c) a central buttress that also provides the radialsupport for the two guide tubes.

In some embodiments, the catheter includes at least two tubular shaftslocated within a distal portion of the catheter body. Each of thetubular shafts can have a distal opening through which one of the atleast two guide tubes is advanced. The catheter can have a closedposition, wherein the distal ends of the distal injection needles arewithdrawn into the at least two guide tubes and the at least two guidetubes are withdrawn into the at least two tubular shafts, wherein theclosed position is configured to prevent needlestick injuries from thedistal injection needles. In some embodiments, the mechanical supportstructure is coupled to a longitudinally movable mechanism. In someembodiments, the catheter can include a fully closed position, the fullyclosed position having the distal end of the injection needles beingwithdrawn into the guide tubes and the guide tubes withdrawn into thetubular shafts, the fully closed position preventing needlestickinjuries from the sharpened distal end of the injection needles. Thelongitudinally movable mechanism can be an obturator.

In some embodiments, the catheter includes three needle guide tubes,three injection needles, and three injector tubes, wherein the distalend of each injector tube coupled to one of the injection needles. Thecatheter can have at least three guide tubes and three injector tubeswith distal injection needles with each injection needle having asharpened distal end. In some embodiments, the mechanical supportstructure can include an obturator movable in the longitudinaldirection. In some embodiments, the mechanical support structure caninclude an intraluminal centering mechanism.

In some embodiments, two guide tubes have a curved distal portion with afirst radius of curvature and the at least two injector tubes withdistal injection needles have a curved distal portion with a secondradius of curvature, wherein the first radius of curvature and secondradius of curvature being preset to within about 40 percent, 35 percent,30 percent, 25 percent, 20 percent, 15 percent, 10 percent, or less ofeach other. In some embodiments, the catheter includes a fixed distalguidewire. In some embodiments, the total internal volume or dead spacefrom a proximal part to a distal end of an infusion flow path of thecatheter is less than about 0.5 ml, 0.4 ml, 0.3 ml, or less. In someembodiments, the catheter includes a radiopaque marker attached to orwithin a portion of one or more of the structures selected from thegroup consisting of: a) the injection needle, b) the guide tubes, c) thecatheter body, and d) the mechanical support structure. The radiopaquemarkers can be operably connected to a portion of one or more of thestructures selected from the group of: a) the injector tubes with distalinjection needles, b) the guide tubes, the mechanical support structureand c) the catheter body.

In some embodiments, the catheter includes a single injection portlocated near a proximal end of the catheter. The single fluid injectionport can be in fluid communication with the fluid injection lumen of thecatheter body. In some embodiments, the catheter includes an injectionport located near a proximal end of the catheter. The fluid injectionport can have a non-standard connector that is a different from anyother fitting on the handle of the catheter. In some embodiments, acustom syringe having a distal end configured to mate with thenon-standard connector is provided. In some embodiments, the cathetercan have a control mechanism adapted to control the movement and outwardexpansion of the two guide tubes. In some embodiments, the catheter canhave an injection needle control mechanism configured to control themovement and outward expansion of the injection needles.

These and other features and advantages of this invention will becomeobvious to a person of ordinary skill in this art upon reading of thedetailed description of this invention including the associated drawingsand the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a longitudinal cross-section of a distal portion of anIntraluminal Nerve Ablation System (INAS) having a fixed guide wire atits distal end.

FIG. 2 is a schematic view of the distal portion of the PTAC in its openposition as it would be manually expanded for delivery of an ablativeagent into the peri-vascular space.

FIG. 3 is a longitudinal cross-section of a distal portion of the PTACof FIG. 2 in its open position as it would be configured for delivery ofan ablative solution into the target vessel wall.

FIG. 4 is an enlargement of region S4 of the PTAC of FIG. 3.

FIG. 5 is an enlargement of region S5 of the PTAC of FIG. 3.

FIG. 6 is a transverse cross-section at section 6-6 of the PTAClongitudinal cross-section enlargement shown in FIG. 5.

FIG. 7 is a transverse cross-section at section 7-7 of the PTAClongitudinal cross-section enlargement shown in FIG. 5.

FIG. 8 is a schematic view of the distal portion of the manuallyexpandable embodiment of the presently disclosed PTAC as it is advancedin its pre-deployment condition out of a guiding catheter into a renalartery.

FIG. 9 is a schematic view of the distal portion of the manuallyexpandable embodiment of the PTAC following manual advancement of theguide tubes against the interior wall of the renal artery.

FIG. 10 is a schematic view of the distal portion of the manuallyexpandable embodiment of the PTAC following advancement of the injectortubes with distal injection needles out of the guide tubes to thedesired depth of penetration beyond the interior wall of the renalartery.

FIG. 11 is a schematic view of the handle that is situated at theproximal region of the PTAC.

FIG. 12 is a cross-section of a distal section of an intraluminalcentering mechanism (ICM) which is an alternative embodiment showing awire basket with radiopaque markers that can be used to provide radialand lateral support for the guide tubes through which injector tubeswith distal needles are advanced against and through the interior wallof a vessel such as the renal artery.

FIG. 13 is an enlargement of the region S13 of the intraluminalcentering mechanism (ICM) of FIG. 12.

FIG. 14 is an enlargement of the region S14 as shown in FIG. 12.

FIG. 15 is a longitudinal cross-section of a distal portion of analternative embodiment where the guide tubes and injector tubes of thePTAC are combined into a single injector tube assembly which is advancedto penetrate the wall of the target vessel.

FIG. 16 is a longitudinal cross-section of still another embodimentwhich uses an inflatable balloon to move outward and provide radial andlateral support for the guide tubes as they engage the interior wall ofthe target vessel.

FIG. 17 is a schematic view of the central buttress component of thePTAC of FIGS. 2 through 11.

FIG. 18 is a longitudinal cross-section of the central portion of thePTAC showing the multiple sections of the inner, middle and outer tubes.

FIG. 19 is a schematic view showing the orientation of the sharpenedinjection needles as they would appear at the distal end of the PTAC.

FIG. 20 is a schematic view of a preferred shape of the sharpenedinjection needles.

FIG. 21A is a schematic view of an alternative embodiment of the PTACwhich uses the proximal portion of the obturator as the supportstructure for the guide tubes and shows the configuration of the PTACafter the guide tubes are advanced but before the needles are advanced.

FIG. 21B is a schematic view of an alternative embodiment of the PTAC inwhich the proximal portion of the obturator provides additional supportfor the guide tubes.

DETAILED DESCRIPTION

FIG. 1 is a longitudinal cross-section of the expanded distal portion ofthe invention by Fischell as described in U.S. patent application Ser.No. 13/643,070 filed on Oct. 23, 2012. This Intra-vascular NerveAblation System (INAS) 50 has a fixed guide wire 20 with tip 28 at itsdistal end. FIG. 1 shows the INAS 10 in its fully open position with theself-expanding guide tubes 15 with coaxial injector tubes 16 withsharpened distal injection needles 19 and needle distal opening 17 whichis the injection egress deployed outward beyond the distal end 29 of theguide tubes 15. It should be understood that this embodiment of the INAS50 has four injector tubes 16 protruding through four guide tubes 15.The guide tubes 15 are the needle guiding elements that help support thethin and flexible injector tubes 16 with distal injection needles 19 asthey are advanced into the wall of a target vessel.

In this configuration, the sheath 22 has been pulled back to allow theguide tubes 15 with radiopaque marker bands 27 to expand outwardly. Ifthe elements 15 and 16 are not fabricated from a radiopaque metal, it isenvisioned that the distal portion of the injector tube(s) 16 and guidetube(s) 15 would be marked with a radiopaque material such as gold ortantalum, or a piece of radiopaque material may be used to form or belocated within the injector tubes 16 or the sharpened needles 19 toprovide better visualization of the deployment of the INAS 50 usingstandard fluoroscopy. FIG. 1 shows a radiopaque wire 18 placed withinthe injector tube 16 to allow fluoroscopy to be used by the operator toclearly identify the position of the injector tubes 16 with distalinjection needles 19. It is particularly important for the operator toknow the location of the injection needles 19 after they have beenadvanced through the wall of the vessel. The material for the radiopaquewire 18 can be selected from well-known radiopaque metals such asplatinum, tantalum or gold or an alloy of that type of metal.

The diameter L1 denotes the memory configuration for the fully openedguide tubes 15. For use in the renal arteries, L1 would typically bebetween 3 and 10 mm with 8 mm being a best configuration if only onesize is made as very few renal arteries have a diameter that is largerthan 7 mm. Also shown in FIG. 1 are the distal ends 29 of the guidetubes 15 that in the fully open configuration have their planes situatedparallel to the longitudinal axis of the INAS 50. The distal portion ofthe INAS 50 has the tapered section 26, radiopaque marker band 24 andproximal portion 23. This tapered unit including elements 23, 24 and 26is called an obturator 30. The obturator 30 is fixedly attached to thecore wire 11 and the outer layer 25 of the guide wire 20. Otherimportant features of this design are the radiopaque marker 13 locatedat the distal end of the sheath 22 that in combination with theradiopaque marker band 24 on the obturator 30, provide indication of therelative position of the distal end of the sheath 22 and the obturator30. When the radiopaque marker 13 located at the distal end of thesheath 22 is in close proximity to the radiopaque marker band 24 of theobturator 30, the operator knows that the guide tubes 15 containing theinjector tubes 16 are fully enclosed. When the radiopaque marker 13 ofthe sheath 22 are fully separated, the operator knows that at least theguide tubes 15 are each deployed outward to have their distal ends 29placed in contact the interior surface of the vessel. Also disclosed inthe Fischell design is that the natural preformed radius of curvature ofthe injector tubes 16 should correspond to that of the guide tubes 15 sothat the guide tubes 15 will maintain their position against theinterior wall of the target vessel as the injector tubes 16 with distalinjection needles 19 are advanced coaxially therethrough to penetratethe wall of the target vessel. As previously discussed, the limitationof this design is that the reliability and stability of unsupportedself-expanding needle guiding element structures such as the guide tubes15 that might not automatically be centered in the target vessel. Inaddition the guide tubes 15 without any additional radial support canback away from the interior wall of the target vessel during advancementof injector tubes 16.

FIG. 2 is a schematic view of the distal portion of a PTAC 100 in itsopen position, showing an outer tube 102, outer tube extension 104having distal openings 131 through which the guide tubes 115 withradiopaque markers 122 are advanced outward from the body of the PTAC100. Also shown is the tapered section 106 and fixed guide wire 110 withdistal tip 109. The injector tubes 116 with distal injection needles 119and needle distal openings 117 are shown in their fully deployedpositions. The openings 131 support the sides of the guide tubes 115 asthe guide tubes 115 are advanced outward before the advancement of theinjector tubes 16 with distal injector needles 119. The PTAC 100 of FIG.2 has three guide tubes with the third tube hidden behind the catheterand not visible in this schematic view. Although the PTAC 100 of FIG. 2has three guide tubes 115, it is envisioned that other embodiments couldhave as few as one or as many as eight guide tubes with an optimumnumber being three or four. A larger diameter target vessel mightsuggest the use of as many as 4 to 8 guide tubes 115 and injector tubes116.

Different shapes are envisioned for the distal openings (or windows) 131in the outer tube extension 104 where the guide tubes 115 exit. Thesepossible shapes include a racetrack design with curved (e.g., round)proximal and distal ends and straight sides in the axial direction, andoval or round shapes. It is also envisioned that there could be amovable flap covering the opening 131 or a slit that could be opened tomake the outer surface of the PTAC smooth for better delivery into therenal artery.

It is an important feature of this invention that the guide tubes 115are needle guiding elements for the ultra-thin injection needles 119.Specifically, prior art such as Jacobson that describe curved needlesthat are advanced outward from a central catheter to penetrate the wallof a target vessel, have needles that are advanced (naked) on their ownfrom the distal end or side of a catheter. Without additional guidingand backup support during advancement, needles that are thin enough toessentially eliminate the risk of bleeding following penetration andwithdrawal from the wall of the artery are generally too flimsy toreliably penetrate as desired into the vessel wall. Thus it isenvisioned that a key aspect of the PTAC 100 of the present applicationis the inclusion of needle guiding elements such as the guide tubes 115that allow the ultra-thin injection needles 119 to be reliably advancedinto the wall of a target vessel to the desired depth.

FIG. 3 is a longitudinal cross-section of a distal portion of the PTAC100 as shown in FIG. 2. The proximal end of FIG. 3 shows the threeconcentric tubes, the outer tube 102, middle tube 103 and inner tube 105which form the central portion and most of the length of the PTAC 100.The outer tube 102 is attached to the outer tube extension 104 which isin turn attached to the tapered section 106. The fixed guide wire 110with core wire 111 and outer layer 113 extends distally from the distalend of the tapered section 106. It should be noted that only part of thelength of the guide wire 110 is shown in FIG. 3, its full length isshown in FIG. 2. Enlargements of the sections S4 and S5 of FIG. 3 areshown in FIGS. 4 and 5 respectively.

FIG. 3 shows the guide tube 115 with radiopaque marker 122 in its fullyadvanced position placed through the opening 131 in the outer tubeextension 104. The interior surface of the outer tube extension 104forms part of the tubular shaft 120 should be made from a stiff materialsuch as a metal or high durometer plastic so that it will be relativerigid as the guide tubes 115 are advanced and retracted.

A preferred embodiment of the PTAC 100 of the present application usesfour different tubular structures instead of just an outer tube 102 andouter tube extension 104. Specifically, the proximal section would be ametal hypotube 82 shown in FIG. 11. The metal hypotube 82 would connectat its distal end to a relatively stiff plastic tube 92 (see FIG. 18)about 20 cm long that would in turn connect to a softer more flexibleplastic tube about 10 cm long which would be the tube 102 shown in FIGS.2-7. The plastic tubes 92 and 102 would typically have the same interiorand outside diameters. The outer tube extension 104 which is the distalend section of the catheter body typically has a slightly larger insidediameter than the soft outer tube 102. The manifold 125 that connectsthe inner tube 105 to the injector tubes 116 is coaxially within theplastic tubes 92 and 102 and at least several centimeters proximal tothe outer tube extension 104 which is the distal end section of thecatheter body of the PTAC 100.

In a preferred embodiment, the middle tube 103 attaches to, a proximalmetal hypotube and the inner tube 105 would also attach to proximalportion formed from a metal hypotube. The structure of these tubes isshown in FIG. 18.

An important aspect of the presently disclosed PTAC 100 is to minimizethe internal volume or “dead space” for the injection path. This reducesthe needed amount of fluid that would be injected into the peri-vascularspace before the ablative fluid is injected. In one version of thedirections for use, the internal volume would first be flushed andfilled with normal saline outside of the body before the PTAC 100 isinserted into the body. Ideally the dead space should be less than 0.3ml and if possible, close to 0.1 ml. Any volume less than 0.5 ml wouldbe helpful to minimize the amount of flushing fluid injected into theperi-vascular space prior to the injection of the ablative fluid.

The central buttress 121 shown in FIG. 3, supports the guide tube 115both as it is pushed distally and after it is fully deployed. The guidetubes 115 can slide along a surface of the central buttress 121 as theyare pushed by the guide tube control mechanism 330. The guide tubecontrol mechanism 330 can advance a plurality of guide tubes 115simultaneously. The guide tubes 115 advance toward the distal end of thePTAC 100 toward the openings 131. The guide tubes 115 can interact witha deflection surface of the central buttress 121 as they are guidedtoward the openings 131. The deflection surface guides the distallymoving guide tubes 115 outward toward the interior wall of the targetvessel.

This central buttress 121 is a mechanical support structure thatprovides radial support for the advanced guide tubes 115 that preventsthe guide tubes 115 from backing away from the interior wall of thetarget vessel as the injector tubes 116 are advanced through the guidetubes 115 forward to their desired position 2-4 mm beyond the interiorwall of the target vessel. In exceptional cases, the injection needles119 at the distal ends of the injector tubes 116 might be advanced asdeep as 8 mm beyond the interior wall of the target vessel. Lateralsupport for the guide tubes 115 is provided by the sides of the openings131 that in combination with the central buttress 121 are key to theradial and circumferential/lateral support both during guide tube 115advancement and outward expansions, and as backup during delivery of theinjection needles 119 through the interior wall of the target vessel.

The central buttress 121 is disposed within the PTAC 100, and in someembodiments, within the outer tube extension 104. The central buttress121 has a smaller diameter than the PTAC 100 and the outer tubeextension 104. The central buttress 121 may be fixed, immobile, and/ornon-expandable relative to the PTAC 100. The distal tip 145 of thecentral buttress 121 can be coupled (e.g., snap fit) with the taperedsection 106. The central buttress 121 may be integrally formed withinthe PTAC 100 (e.g., the central buttress 121, the distal openings 131,and/or the tapered section 106 could be a single component molded ormachined).

The buttress 121 may comprise a deflection surface, such as a curved orlinear ramp. In some embodiments, the deflection surface issubstantially parallel, parallel, substantially coaxial or coaxial tothe longitudinal axis of the PTAC 100. In other embodiments, thedeflection surface can be substantially perpendicular, perpendicular,substantially offset, offset, substantially angled, or angled to thelongitudinal axis of the PTAC 100. The deflection surface and thelongitudinal axis of the PTAC 100 may form an angle of, for example,approximately 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70degrees, between 30-50 degrees, and in some embodiments 45 degrees. Thedeflection surface can be substantially curved. In some embodiments, thedeflection surface includes a concave surface. The deflection surfacemay include a convex surface near the proximal end of the PTAC 100 and acomplementary concave surface near the distal end of the PTAC 100. Thecurved or concave surface may correspond to the radius of curvature ofthe distal surface of the guide tube 115. The deflection surface mayform a lumen. The lumen may be curved, bowed, linear, or non-linear. Thelumen may correspond to the radius of curvature of the distal surface ofthe guide tube 115.

The deflection surface may be configured to direct the guide tubes 115toward the distal openings 131. The distal openings 131 are located ontubular shaft 120. The number of distal openings 131 may correspond tothe number of guide tubes 115 (e.g., 1:1 ratio), or the number of distalopenings 131 may be more or less than the number of guide tubes 115. Thedistal openings 131 may abut the deflection surface. In someembodiments, the distal openings 131 are the same size and/or shape asthe lumen, and in other embodiments, the distal opening is larger orsmaller than the lumen. The distal portion of the central buttress 121is shown in greater detail in FIG. 17.

The deflection surface of the central buttress 121 and the distalopenings 131 the tubular shaft 120 also provide lateral support thatfacilitates outward expansion purely in the radial direction for theguide tubes. Although the buttress 121 provides both radial and lateralsupport for the guide tubes 115, other embodiments as described hereinmay provide only radial support or only lateral support. Radial supportfor the guide tubes 115 is defined herein as being support for the guidetubes 115 in a direction that is perpendicular to the longitudinal axisof the PTAC 100. Lateral support for the guide tubes 115 is definedherein as being support for the guide tubes 115 in a circumferentialdirection that is perpendicular to the radial direction.

It is also an important feature that the radius of curvature of thedistal portion of the injector tubes 116 have a central axis with thesame, or nearly the same, radius of curvature as the central axis of theguide tubes 115 and of the central axis of the distal portion of thetubular shaft 120 that is formed within the central buttress 121 whenmeasured in an unconstrained state. In addition, the length of the guidetubes 115 should be at least as long as the distal curved portion of theinjector tubes 116 with distal needles 119. This design constrains thecurved portion of each injector tube 116 within the lumen of the guidetube 115 so that the injector tube 116 cannot twist or change position.

The preformed radius of curvature of the injector tubes 116 can besimilar to that of the guide tubes 115 so that the guide tubes 115 willmaintain their position against the interior wall of the target vesselas the injector tubes 116 with distal injection needles 119 are advancedto penetrate the interior wall of the target vessel. Specifically, theradius of curvature of the central axis of the distal portion of theinjector tube 116 can be approximately the same as the radius ofcurvature of the central axis of the guide tube 115. The radii ofcurvature of the central axes of the guide tubes 115 and the injectortubes 116 can be within 1 mm of each other, or within 0.2 mm of eachother in some cases. Although a curved shape with a single radius ofcurvature is shown in FIG. 13, curved shapes of the guide tubes 115 andinjector tubes 116 could have two or more portions each with a differentradius of curvature. Even if two or more different radii of curvatureare used for these components, it can be advantageous that when fullydeployed, the curved shape of the injector tube 116 is such that itslongitudinal axis is coaxial to the longitudinal axis of the lumen ofthe curved portion or portions of the guide tube 115. In other words,the advanced injector tube 116 can in some embodiments fit perfectlywithin the advanced guide tube 115. It is also envisioned that if theradii of curvature are significantly different then the radius ofcurvature of the injector tube 116 can be less than the radius ofcurvature of the guide tube 115 so that when the injector tube 116 isadvanced it will not push the guide tubes 115 away from the interiorwall of the vessel. Another way to characterize the two radii ofcurvature is that they can be, in some cases, within about 20% of eachother and ideally, in some embodiments within about 5%.

As seen in FIG. 3 the inner tube 105 with fluid injection lumen 133connects through the manifold 125 to the three injector tubes 116, thusthe lumens of the injector tubes 116 are in fluid communication with thelumen 133. The inner tube 105 and manifold 125 can slide along thelongitudinal axis of the PTAC 100 inside of the middle tube 103 which isshown with uniform diameter over its length including the portioncoaxially outside of the manifold 125.

It is clear from the drawing of FIG. 3 that the manifold 125 is locatedwithin the lumen of the inner tube 105 in a portion of the tube 105 thatis proximal to the distal end of the tube 105. The inner tube 105 andmanifold 125 are both located coaxially within the outer tube 102 of thePTAC 100 at a position proximal to the outer tube extension 104 which isthe distal end section of the outer body of the PTAC 100. This differssignificantly from the embodiment shown in FIG. 3 of the Jacobson U.S.Pat. No. 6,302,870 where the manifold that connects the tube to theneedles is attached to the distal end of the tube (instead of beinginside it and proximal to the distal end). In addition the Jacobsonmanifold lies coaxially within the distal end section of the outer bodyof the catheter (instead of being in the tube that is proximal to thedistal end section of the catheter). The distal end section beingdefined as that distal portion of the catheter from which the needlesemerge to curve outward into the wall of a vessel.

An important feature of the PTAC 100 can be that the flow rate throughthe needle distal opening 117 for each needle 119 of the PTAC 100 ofFIGS. 2 through 4 is approximately the same. This can most easily beaccomplished by pre-testing each injector tube 116 with injection needle119 and measuring the flow rate, and thus the flow resistance under agiven pressure. Injector tubes 116 would be sorted according to resultsof the testing and the injector tubes selected for each PTAC 100 wouldbe so matched in order to have approximately the same flow resistance.

FIG. 4 is the enlargement of section S4 of the longitudinalcross-section of the PTAC 100 as shown in FIG. 3. FIG. 4 shows thedetails of the guide tubes 115 with interior layer 123, outer layer 127,distal end 129 and radiopaque marker 122. Coaxially within the lumen ofthe guide tube 115 is the injector tube 116 with distal injection needle119, distal opening 117 and radiopaque marker wire 118. The radiopaquemarker wire 118 serves two purposes, first it provides fluoroscopicvisibility of the injector tubes as they are advanced to their positionfor delivery of the ablative fluid into the peri-vascular space into anddeep to the adventitia of the target vessel. Second—marker wire 118reduces the internal volume of the injector tube 116, and thus reducesthe amount of saline required to flush all of the ablative fluid out ofthe PTAC 100 into the peri-vascular space leaving only harmless salinein the PTAC 100 as it is retracted back into the renal artery.Radiopacity of the injector tubes 116 with distal needles 119 is veryimportant so that the operator can confirm under fluoroscopy that theneedles 119 have properly deployed into the wall of the target vessel.Other embodiments of the present disclosure may use coatings, plating ormarkers on the outside and/or inside of the injector tube 116 and needle119 or the injector tube 116 with distal needle 119 could be made from atwo layer clad material. For example, nitinol tubing clad over aplatinum inner tube and then shape set would be ideal as it would bequite visible and eliminate the need for the added marker wire 118 shownin FIGS. 3 and 4.

The guide tubes 115 are advanced and refracted through the tubular shaft120 with distal opening 131. The three guide tubes 115 are attached toeach other near their proximal ends by the guide tube connector 132.FIG. 4 also clearly shows how the guide tube 115, when advanced againstthe central buttress 121 is forced outward and is supported by thecurved ramp 144 of the central buttress 121 as well as the sides of theopening 131 of the tubular shaft 120. The central buttress 121 also hasproximal fingers 142 that provide additional lateral support for theguide tubes 115.

The outer tube extension 104 connects at its distal end to the taperedsection 106 which in turn lies coaxially around the guide wire 110 withcore wire 111 and outer layer 113.

Also shown in FIG. 4 is the penetration depth L2 which is the distancefrom the distal end 129 of the guide tube 115 to the center of thedistal opening 117 located at the distal end of the injection needle119. Mechanisms at the proximal end of the PTAC 100 (as shown in FIG.11) control both the motion of the distal components such as theinjector tubes 116 and guide tubes 115 as well as to limit and/or adjustthe penetration depth L2 of the needles 119.

It is envisioned that the central buttress 121 and distal openings 131can, as shown in FIG. 4, be separate components of the PTAC 100 or theycan be formed as a single molded or machined part as is shown in FIG.17. The distal tip 145 of the central buttress 121 provides theattachment to secure the buttress 121 to the tapered section 106.Additionally, 121, 131, and 106 could be a single component molded ormachined.

While the preferred embodiment of the PTAC 100 has the guide tubes 115with a pre-formed curved shape, flexible naturally straight guide tubesare also envisioned where the buttress 121 forces the straight guidetubes to curve outward against the interior wall of the target vessel.

While the term “central buttress” will be used herein, the key componentof the buttress 121 is the ramp 144 that provides radial and somelateral support for the deployed guide tubes 115. Specifically, thecurved ramp 144 of the buttress 121 supports and guides the outwardmotion of the guide tubes 115 as they exit though the distal openings131 and also provide radial support for the guide tubes 115 andinjection tubes, as they engage the interior wall of the target vessel.Additional lateral support is provided by the fingers 142 of the centralbuttress 121.

The shape of the ramp 144 or the buttress 121 may include proximalextensions or fingers that create a smooth curved or inclined surface tosteer the guide tubes 115 outward as the guide tubes 115 are advanceddistally through the opening 131.

While the central buttress shown in FIG. 4 is a plastic part, aradiopaque metal part, such as stainless steel, or a plastic materialthat includes a radiopaque filler such as tungsten could beadvantageously employed for showing the exact location where the guidetubes 115 will exit the PTAC 100. It is also envisioned that aradiopaque marker could be placed or attached to a portion of theopenings 131 or buttress 121 or outer tube extension 104 to show thelikely spot where the guide tubes 115 and thus the injection needles 119would engage the interior wall of the target vessel.

Many of the components of the PTAC 100 are typically made from plasticmaterials such as polyamide, polyurethane, nylon or tecothane. Theseinclude the outer tube 102, middle tube 103 and inner tube 105, theouter tube extension 104, inner layer 127 and outer layer 123 of theguide tubes 115, the tapered section 106, the buttress 121, the guidetube connector 132 and the manifold 125. The manifold 125 can be amolded part or be epoxy or another resin that is injected to glue theinjector tubes together within the lumen of the inner tube 105.

It is also envisioned that any or all of the inner tube 105, middle tube103 or outer tube 102 could also be a metal hypotube or a metalreinforced plastic tube.

The injector tubes 116 would typically be made of a springy or shapememory metal such as nitinol. The radiopaque wire 118 and guide tuberadiopaque marker 122 would be made of a radiopaque material such asgold, platinum or tantalum or an alloy of these or similar metals. Thecore wire 111 would typically be stainless steel and the outer layer 113would be wrapped platinum or platinum iridium wire. The outer layercould also be a polymeric material. Any or certain portions of theoutside of the PTAC 100 could be lubricity coated to provide improvedperformance. The injector tubes 116 and injection needles 119 should besmaller than 0.5 mm in diameter and preferably less than 0.3 mm indiameter to avoid any blood loss or leakage as the needles penetrateinto the wall of the target vessel and are then removed.

FIG. 5 is the enlargement of section S5 of FIG. 3 showing the transitionfrom the central portion to the distal portion of the PTAC 100 includingthe outer tube 102, middle tube 103 and inner tube 105 with injectionlumen 133. Also shown is the connection between the outer tube 102 andthe outer tube extension 104. While the manifold 125 in FIG. 5 shows theproximal end of the injector tubes 116 at a position distal to theproximal end of the manifold 125, it may be preferable for manufacturingthe PTAC 100 with the proximal end of the injector tubes 116 located ator proximal to the proximal end of the manifold 125.

The guide tube connector 132 connects the three guide tubes 115 to themiddle tube 103 that provides the impetus for advancement and retractionof the three guide tubes 115. The motion of the middle tube 103 isproduced by the motion of control mechanisms at the proximal end of thePTAC 100. The manifold 125 lies inside of the distal portion of theinner tube 105 and connects together the three injector tubes 116 sothat advancement and retraction of the inner tube 105 providessimultaneous advancement and retraction of the injector tubes 116. Alsoshown in FIG. 5 are the flushing spaces between the several tubes.Specifically shown is the outer annular space 137 between the middletube 103 and the outer tube 102 and the inner annular space 139 betweenthe inner tube 105 and the middle tube 103. Each of these spaces 137 and139 are to be flushed through with normal saline solution prior toinsertion of the PTAC 100 into the patient's body.

It is also visible in FIG. 5 how the proximal end of the injector tube116 is in fluid communication with the injection lumen 133 of the innertube 105. The radiopaque wire 118 which lies within the lumen of theinjector tube 116 extends proximally from the proximal end of theinjector tube 116 and is connected into the body of the manifold 125. Itis also envisioned that instead of connecting into the body of themanifold 125, the three radiopaque wires could be welded together and/orattached to the proximal end of the manifold 125. Longitudinal motion ofthe inner tube 105 within the uniform diameter middle tube 103 causesthe manifold 125 and attached injector tubes 116 to also movelongitudinally. This longitudinal motion caused by control mechanismsnear the proximal end of the PTAC 100 will advance and retract theinjector tubes 116 through the lumens of the guide tubes 115 to expandoutwardly to penetrate the wall of the target vessel to facilitatedelivery of the ablative fluid.

FIG. 5 also shows how the three injector tubes 116 extend from thedistal end of the inner tube 105 and manifold 125 and then enter thelumen of the inner layer 127 of the guide tube 115 at the proximal endof the guide tube 115. The guide tubes 115 and guide tube connector 132are attached coaxially within the distal section of the middle tube 103.Thus longitudinal motion of the middle tube 103 will cause longitudinalmotion of the guide tube connector 132 and guide tubes 115 thus allowingthe mechanism at the proximal section of the PTAC 100 to advance andretract the guide tubes 115 with respect to the outer tube 102 and outertube extension 104.

It is also envisioned that the penetration depth limitation could be amechanism that limits the forward motion of the distal end of the innertube 105 with respect to the guide tube connector 132. A ring or otherstructure situated between the distal end of the inner tube 105 ormanifold 125 and the proximal end of the guide tube connector 132 wouldlimit the forward (distal) motion of the distal end of the inner tube105 and thus limit penetration of the needles 119 beyond the distal ends129 of the guide tubes 115. Such a structure could be unattached, orattached to an internal structure of the PTAC 100 shown in FIG. 5 suchas the inner tube 105, manifold 125, injector tubes 116, guide tubeconnector 132, proximal ends of the guide tubes or the middle tube 103.Such a structure could also have a length adjustment such as screwthreads that would allow it to be used to adjust the penetration depthof the needles 119 beyond the distal ends 129 of the guide tubes 115.

FIG. 6 is a transverse cross-section at section 6-6 of the PTAC 100 asshown in FIG. 5. FIG. 6 shows the coaxial components of the main body ofthe PTAC 100 including the outer tube 102, the middle tube 103, theinner tube 105, the annular space 137 between the outer tube 102 and themiddle tube 103 and the annular space 139 between the middle tube 103and the inner tube 105. It also shows how the manifold 125 connectstogether the three injector tubes 116 with radiopaque wires 118 insideof the inner tube 105.

FIG. 7 is a transverse cross-section at section 7-7 of the PTAC 100 asshown in FIG. 5. FIG. 7 shows the coaxial orientation of outer tube 102which connects distally to the outer tube extension 104 which liesoutside of the middle tube 103. The guide tube connector 132 connectsthe three guide tubes 115 with inner plastic layer 127 that is situatedinside of the guide tube connector 132 that is itself situated insidethe middle tube 103. This construction allows the longitudinal motion ofthe middle tube 103 to cause similar motion in the connected guide tubeconnector 132 and guide tubes 115.

FIGS. 8-11 are a set of schematic views that illustrate how the PTAC 100is used for peri-vascular renal denervation. FIG. 8 shows a schematicview of a distal portion of the PTAC 100 in its pre-deploymentconfiguration with outer tube 102, outer tube extension 104, taperedsection 106 and distal fixed guide wire 110 with distal end 109. Two ofthe three distal openings 131 are also shown on the surface of the outertube extension 104. In FIG. 8, the distal portion of the PTAC 100 hasbeen pushed out of the distal end of the renal guiding catheter 140 to aposition within the renal artery. Also shown are the Internal ElasticLamina (IEL), media, External Elastic Lamina (EEL) and the adventitia ofthe renal artery and aorta. The PTAC 100 includes the central buttress121 and the outer tube extension 104 located within a distal portion ofthe catheter body. Each of the central buttress 121 and the outer tubeextension 104 have a distal opening through which one of the at leasttwo guide tubes 115 is advanced outwardly against the interior wall ofthe target vessel. The PTAC 100 further includes a closed position. Theclosed position has the distal end of the injection needles 119 beingwithdrawn into the guide tubes 115 and the guide tubes withdrawn 115into the distal openings. The closed position can be an advantageoussafety feature, and prevents needlestick injuries form the sharpeneddistal end of the injection needles 119.

FIG. 9 shows a schematic view of a distal portion of the PTAC 100 withina renal artery with the guide tubes 115 fully expanded outwardly againstthe interior wall of the artery. The guide tubes 115 can beself-expanding and move outward against the inside wall of the targetvessel. The guide tubes are movable distally and proximally with respectto the distal portion of the PTAC 100. The guide tubes are manuallymovable and expandable. The longitudinal motion of the middle tube 103,see FIG. 5, can cause longitudinal motion of the guide tube connector132 and guide tubes 115 thus allowing the mechanism at the proximalsection of the PTAC 100 to advance and retract the guide tubes 115 withrespect to the outer tube 102 and outer tube extension 104. The guidetubes 115 are supported radially and/or laterally by the buttress 121.In some embodiments, the guide tubes 115 interact with a deflectionsurface of the buttress 121 to deflect outward and through the openings131.

The renal artery and aorta are shown in cross-section so the lower guidetube 115 is actually touching a portion of the interior wall of therenal artery that is not shown because of the cross-section which splitsthe renal artery at 0 and 180 degrees. The third guide tube 115 is notseen as it is hidden behind the PTAC 100 but it too touches the interiorsurface of the renal artery wall. The radiopaque markers 122 on theguide tubes 115 allow the operator to visualize that the fully expandedguide tubes 115 are actually in contact with the interior wall of therenal artery. When the three guide tubes 115 are advanced outward, oneguide tube 115 will touch the interior wall of the target vessel firstand as the guide tubes are further advanced outward, this first touchingguide tube will push the body of the PTAC 100 away from the wall towardthe center of the vessel until the second guide tube 115 touches theinterior wall of the target vessel. Then both touching guide tubes 115will push the PTAC 100 further toward the center of the vessel until thethird guide tube 115 touches the interior wall of the vessel. Becausethe guide tubes here each the same diameter of expansion from thelongitudinal axis of the PTAC, this will reproducibly place the distalportion of the PTAC 100 close to the true center of the vessel.Fluoroscopic imaging of the radiopaque markers on the distal portion ofthe guide tubes provides visual confirmation of the correct centering ofthe guide tubes. This centering can also be confirmed by using contrastinjected from the guiding catheter, after guide tube deployment. Aftercentering, the guide tubes 115 are flush against the inside wall of thetarget vessel. It can in some cases be advantageous to have the guidetube flush against the inside wall of the target vessel to provide themost radial and/or lateral support for the injector tubes 116 withdistal injection needles 119. By providing radial and/or lateral supportfor the injector tubes 116 up to the inside wall of the target vessel,the distal injection needles 119 can be thin needles that will not causeblood loss. The thin needles may be flimsy and need such radial and/orlateral support provided by the guide tubes 115.

Of significance is that the emergence of the guide tubes 115 from theopenings 131 in the outer tube extension 104 provides lateral supportfor the guide tubes 115 as they deploy outward. Radial support isprovided by the central buttress 121 shown in FIG. 4. Together theradial and lateral support for the guide tubes are extremely importantin having the guide tubes expand uniformly resulting in a well centereddistal portion of the PTAC 100 that is ready for deployment of theinjection needles 119 seen in FIG. 10.

The PTAC 100 can include central buttresses, obturators and/orintraluminal centering mechanisms which provide lateral and/or radialsupport for the guide tubes 115. The mechanical support can be compactand/or longitudinally extending, reducing the diameter of the PTAC 100.The PTAC 100 is designed to allow much better blood flow. The cathetercan be moved through the vessel without obstructing the blood flowthrough the vessel. In some embodiments, less than about 70%, 65%, 60%,55%, 50%, 45%, 40%, 35%, 30%, 25%, or less of the cross-sectional lumenof the of the cross sectional area of the lumen of the target vessel isobscured. In some embodiments, the PTAC 100 obstructs less than 50% ofthe diameter and/or cross sectional area of the lumen, to prevent orminimize ischemia to distal organs and/or tissues. For Renal Denervationtherapies for the treatment of hypertension, maintaining adequate bloodflow to the kidneys, which in many cases are already somewhatcompromised, can be important.

The guide tubes 115 can be expanded without obstructing or substantiallyobstructing the blood flow through the lumen. As shown in FIG. 10, theblood can flow around the PTAC 100 and around the guide tubes 115. Insome embodiments, the mechanical support is not located externally fromthe PTAC 100, but rather, the mechanical support is disposed within thePTAC 100. The emergence of the guide tubes 115 from the openings 131 inthe outer tube extension 104 provides lateral support for the guidetubes 115 as they deploy outward. Lateral and/or radial support isprovided by the central buttress 121 shown in FIG. 4. The lateralopenings 131 and the central buttress 121 provide sufficient radial andlateral support for the guide tubes without obstructing blood flowaround the PTAC 100.

FIG. 10 shows a schematic view of a distal portion of the PTAC 100within a renal artery with the injector tubes 116 with distal injectionneedles 119 fully deployed to deliver an ablative fluid into theperi-vascular space within and/or deep to the adventitia of the renalartery. The injector tubes 116 traverse the lumen of the guide tubes115, and follow the curvatures of the guide tubes 115, toward theinterior wall of the artery. The injector tubes 116 are supportedlaterally and/or radially by the guide tubes 115, the lateral openings131, and the central buttress 121. The injector tubes 116 are expandedinto the interior wall of the artery. In some embodiments, the needledistal openings 117 at or near the distal end of the injection needles119 should be positioned beyond the EEL and toward the outside of theadventitia as shown for the upper needle 119 in FIG. 10. The thirdneedle 119 and guide tube 115 are hidden behind the body of the PTAC 100so they do not appear in FIG. 10. The sympathetic nerves which are thetarget for renal denervation lie within the adventitia or within severalmillimeters outside of the adventitia. Specifically a distance of 2-4 mmbeyond the IEL is the appropriate position for the needle distal opening117. If the sympathetic nerves are deeper, it is also envisioned thatdepths of 4 to 8 mm could be used.

The injection needle control mechanism 340 allows the user of the PTAC100 to control the distal and proximal motion of the injector tubes 116with distal injection needles 119. As mentioned above with respect toFIG. 9, the guide tubes 115 can each abut the tissue wall andreproducibly place the distal portion of the PTAC 100 close to the truecenter of the vessel. The injection needle control mechanism 340 canadvance a plurality of injector tubes 116 simultaneously. The injectortubes 116 advance beyond the guide tubes 115 and into the tissue. Thecentering of the PTAC 100 can ensure that each injector tube 116simultaneously advances to the same depth within the tissue. Withpredictable catheter centering, guide tube expansion, and injectionneedle expansion, the PTAC 100 achieves accurate and reproducible needlepenetration to a targeted depth. Adjustment of the penetration depth bymechanisms in the proximal end of the PTAC may be eitherphysician-controlled or they could be preset during device production.The depth limitation feature of some embodiments has the distal openingof the needles set to be a fixed distance beyond the distal end of theguide tubes. This prevents each needle from being accidentally set todifferent depths. The simpler design of the present application allowsthe needles to be delivered to equal depths.

FIG. 11 is a schematic view of an embodiment of the proximal section 300(or handle) of the PTAC 100 having control mechanisms for advancing andretracting the needle guiding elements/guide tubes 115 and injectortubes 116 with distal needles 119 during the procedure to delivery anablative fluid to the peri-vascular space. The handle 300 also haslocking mechanisms activated by first and second controls such aspress-able buttons 332 and 342. Specifically, button 332 when depressedunlocks the motion of the guide tube control cylinder 333 with respectto the outer tube control cylinder 335. The outer tube control cylinder335 is attached to the outer tube 102. The transition section 338provides strain relief to avoid kinks at the connection between theouter tube control cylinder 335 and the outer tube 102. The guide tubecontrol cylinder 333 is attached to the middle tube 103 of FIGS. 2-7that in turn is connected to the guide tubes 115 of FIGS. 2 through 10.

The guide tube control mechanism 330 allows the user of the PTAC 100 tocontrol the distal and proximal motion of the guide tubes 115 andincludes the button 332 and the guide tube control cylinder 333. Thebutton 332 when depressed, unlocks the motion of the guide tube controlcylinder 333 with respect to the outer tube control cylinder 335. Thiswill allow the relative longitudinal motion of the middle tube 103 withrespect to the outer tube 102 of FIGS. 3 through 7 which causes theadvancement and retraction of the guide tubes 115. By pressing button332 and/or pushing the guide tube cylinder 333 forward, the operator cancause the guide tubes 115 to move distally within the PTAC 100, interactwith the buttress 121, and/or expand outward from the openings 131.

The injection needle control mechanism 340 allows the user of the PTAC100 to control the distal and proximal motion of the injector tubes 116with distal injection needles 119 and includes the button 342 and theneedle control cylinder 345. The button 342 when depressed, unlocks themotion of the needle control cylinder 345 with respect to the guide tubecontrol cylinder 333. This will allow the relative longitudinal motionof the inner tube 105 with respect to the middle tube 103 of FIGS. 3through 7 which causes the advancement and retraction of the injectortubes 116 with distal injection needles 119 though the guide tubes 115.By pressing button 342 and/or pushing needle control cylinder 345forward, the operator can cause the injector tubes 116 to move distallywithin the PTAC 100, interact with the buttress 121, and expand outwardfrom the openings 131, traverse the lumen of the guide tubes 115, and/orexpand outward from the end of the guide tubes 115.

The handle 300 shown in FIG. 11 has the flushing port 344. Port 344,which would typically have a Luer fitting, is shown with a cap 346. Port344 is used to flush with saline the annular spaces 137 and 139 as shownin FIGS. 5 and 6. The injection port 354 which typically has an ablativefluid connector fitting is shown with cap 356. Port 354 allows injectionof the ablative fluid into the lumen 133 of FIGS. 3 and 5 which is influid communication with the lumens of the injector tubes 116 which arein fluid communication with the needle distal openings 117.

Although FIG. 11 shows one flushing port 344, it envisioned that two ormore flushing ports could be used to flush the internal spaces (otherthan the injection lumen) within the PTAC 100. It is also envisionedthat a single button and cylinder mechanism could replace the twobuttons 332 and 342. If this is the case, then a telescoping mechanism,internal to the proximal portion of the PTAC 100 would, upon advancementof the single button, first advance the guide tubes 115 then advance theinjector tubes 116 with distal needles 119. Retraction of the singlebutton would first retract the needles 119 and then retract the guidetubes 115.

While a standard Luer or Luer lock fitting could be used for theablative fluid connector fitting for the injection port 354, in someembodiments of the presently disclosed PTAC 100, that a non-standardfitting can be used for injection of the ablative fluid. In other words,the non-standard fitting is different than the fitting of the flushingports 344 and in some embodiments is a fitting other than the standardLuer or Luer lock fitting. The non-standard fitting can be a uniqueshape (e.g., square, triangular, oval, oblong, trapezoidal, irregularpolygon, regular polygon, etc.). The non-standard fitting can have aunique coupling between the fitting and the mating syringe (e.g., key,detent, twist-lock, snap-fit, etc.). The non-standard fitting can have aunique size (e.g., larger or smaller diameter than the other fittings onthe handle). Because of the ablative/toxic nature of the ablative fluid,having a non-standard fitting for the port 354 would reduce the chanceof accidentally injecting the ablative fluid into one of the other ports(e.g. 344) or into the standard Luer fitting in the “Y” adaptertypically used with a renal guiding catheter. It would also prevent theoperator from the potential error of injecting flushing solution orother agents contained in a conventional Luer lock syringe, through thelumen of the injection tubes. It would also be an advantage for thenon-standard fitting port 354 to have a smaller lumen than a standardLuer fitting so as to minimize the catheter dead space/internal volume.

A custom syringe with the non-standard fitting of the opposite sexdesigned to connect to the port 354 would be provided separately orwithin the PTAC 100 package. Such a syringe could contain exactly thecorrect volume for the appropriate amount of ablative fluid to achieverenal denervation, for example 0.25 ml of ethanol. Because the volume oftissue to be treated will vary with the diameter of the renal artery,several syringes of volumes ranging from 0.1 ml to 0.5 ml may beprovided, each with a non-standard connector to connect to the injectionport 354. If saline flushing, or the injection of other fluids (e.g.,contrast or an anesthetic) are part of the procedure, additionalsyringes could be provided that contain the appropriate volume and typeof fluid for visualization, flushing, renal denervation or for painrelief. It is envisioned that the ablative solution fluid injectionsyringe with a non-standard fitting could have a different color ordistinct marking indicia as compared to the syringe for flushing througha port such as the port 344.

The handle 300 also includes a gap adjustment cylinder 348 that whenrotated in one direction reduces the penetration depth L2 shown in FIG.4 which is the distance the injection needles 119 extend beyond thedistal ends 129 of the guide tubes 115. Rotation in the other directionof the cylinder 348 will increase the penetration depth L2. It isenvisioned that the gap adjustment cylinder 348 could be accessible tothe user of the PTAC 100 with markings on the handle 300 to indicate thedistance that will be achieved. In a preferred embodiment of the handle300, the gap adjustment cylinder 348 could be accessible only duringassembly and testing of the PTAC 100 at the factory. This fabricationmethod is designed to ensure a properly calibrated penetration depth L2of FIG. 4 that is preset in the factory during manufacturing and testingof each PTAC 100. This ability to accurately set and calibrate thepenetration depth L2 is critical to a good yield during manufacturing.In other words, even with variation of a few millimeters in the relativelengths of the components of the PTAC 100 such as the inner tube 105 andmiddle tube 103, the distance L2 can be dialed in exactly using the gapadjustment cylinder 348. In this preferred embodiment, the PTAC 100would be labeled according to the penetration depth L2 shown in FIG. 4.For example, the PTAC 100 might be configured to have three differentdepths L2 of 2.5 mm, 3 mm and 3.5 mm. It is also envisioned that a setscrew or other mechanism (not shown) could be included to lock the gapadjustment cylinder 348 at the desired penetration depth setting. Whilea gap adjustment cylinder 348 is shown here, it is envisioned that othermechanisms such as a sliding cylinder could also be used to adjust thedepth L2.

The function of the handle 300 is to operate the PTAC 100 forPeri-Vascular Renal Denervation (PVRD). This procedure would include thefollowing steps although not every step is essential and steps may besimplified or modified as will be appreciated by those of skill in thisart:

-   -   1) Flush all of the internal volumes of the PTAC 100 with normal        saline through the ports 344 and 354.    -   2) Insert the PTAC 100 through a previously placed guiding        catheter 140 of FIGS. 8 through 10, positioning the distal        portion of the PTAC 100 as shown in FIG. 8 at the desired        location in one patient's renal artery.    -   3) Depress the button 332, and while holding the outer tube        control cylinder 335 which is locked to the guide tube control        cylinder 333, push the guide tube control cylinder 335 in the        distal direction until the notch 331 engages the port 344        limiting the advance of the middle tube 103 of FIG. 5 and fully        deploying the guide tubes 115 from inside the tubular shafts 120        and out through the openings 131 as shown in FIG. 9.    -   4) Release the button 332 which relocks the relative motion of        the outer tube control cylinder 335 with respect to the guide        tube control cylinder 333.    -   5) Depress the button 342 that allows relative motion of the        injection needle control cylinder 345 with respect to the guide        tube control cylinder 333 and while holding the outer tube        control cylinder 335 (which is now locked to the guide tube        control cylinder 333) advance the needle control cylinder 345        with distal end 349 until the penetration limiting mechanism        stops the motion and the preset depth L2 of the needles 119 with        respect to the distal ends 129 of the guide tubes 115. There are        two ways this can be done: 1) The distal end 349 of the needle        control cylinder 345 is pushed forward until it engages the        guide tube flush port 344 or 2) the internal gap 347 is closed        against the proximal end of the gap adjustment cylinder 348        inside the needle control cylinder 345.    -   6) Release the button 342 which relocks the motion of the        injection needle control cylinder 345 to the guide tube control        cylinder 333. This places the PTAC 100 in the configuration        shown in FIG. 10 where the needles 119 penetrate through the        internal elastic lamina (IEL) and penetrate to a preset distance        (typically between 0.5 to 4 mm but preferably about 2-4 mm)        beyond the IEL into the vessel wall of the renal artery. The        depth of 2-3 mm will minimize intimal and medial renal artery        injury. Depths as high as 8 mm may be needed for some unusual        target vessels.    -   7) In this position a syringe or manifold with syringes (not        shown) can be attached to the port 354 and the desired volume of        ablative fluid is injected. The ablative agent which can be an        ablative fluid, such as ethanol (ethyl alcohol), distilled        water, hypertonic saline, hypotonic saline, phenol, glycerol,        lidocaine, bupivacaine, tetracaine, benzocaine, guanethidine,        botulinum toxin, glycosides or other appropriate neurotoxic        fluid. This could include a combination of 2 or more        neuroablative fluids or local anesthetic agents together or in        sequence (local anesthetic first to diminish discomfort,        followed by delivery of the ablative agent) and/or high        temperature fluids (or steam), or extremely cold (cryoablative)        fluid into the vessel wall and/or the volume just outside of the        vessel. A typical injection would be 0.1 to 5 ml. This should        produce a multiplicity of ablation zones (one for each injection        needles 119) that will intersect to form an ablative ring around        the circumference of the target vessel. Contrast could be added        to the injection either during a test injection before the        neuroablative agent or during the therapeutic injection to allow        x-ray visualization of the ablation zone. With ethanol, as an        ablative agent, a volume of less than 0.5 ml is sufficient for        this infusion as it will not only completely fill the needed        volume including the sympathetic nerves, but is small enough        that if accidentally discharged into the renal artery, would not        harm the patient's kidneys. Ideally, a volume of 0.1 ml to 0.3        ml of ethanol should be used. The amount used could be the same        for all renal arteries or it could vary depending on the        diameter of the renal artery into which the ethanol is to be        injected. The agrophobic and lipophilic nature of ethanol        enhances the spread allowing such a small volume to be        effective. It is desirable to fluoroscopically verify the        deployment of the needles 119 of FIGS. 2-4 into the vessel wall        of the target vessel before injecting the ablative agent or        fluid.    -   8) Next a syringe with normal saline solution is attached to the        port 354 replacing the ablative fluid syringe. Ideally, slightly        more saline is injected than the total volume of dead space to        ensure there is no ablative fluid left in the PTAC 100. For        example, if the dead space in the PTAC 100 is 0.1 ml then for        example 0.1-0.15 ml of saline would be a good amount to ensure        the ablative fluid is all delivered through the needle distal        openings 117 of the injection needles 119 of FIG. 10 to the        appropriate peri-vascular volume of tissue.    -   9) Depress the button 342 and while holding the outer tube        control cylinder 335, pull the needle control cylinder 345 back        in the proximal direction until the injection needles 119 are        fully retracted back into the guide tubes 115. It is envisioned        that a click or stop would occur when the injection needle        control cylinder 345 reaches the correct position so that the        injection needles 119 are fully retracted.    -   10) Release the button 342 locking the motion of the injection        needle control cylinder 345 to the guide tube control cylinder        333.    -   11) Depress the button 332 releasing the relative motion of the        outer tube control cylinder 335 with respect to the guide tube        control cylinder 333 that is now locked to the injection needle        control cylinder 345.    -   12) Retract in the proximal direction the guide tube control        cylinder 333 with respect to the outer tube control cylinder        335. This will retract the guide tubes 115 of the configuration        of FIG. 9 back inside the openings 131 in the outer body        extension 104 the PTAC 100.    -   13) Pull the PTAC 100 back into the guiding catheter 140.    -   14) Move the guiding catheter 140 to the other renal artery.    -   15) Repeat steps 3 through 13 for the other renal artery.    -   16) Remove the PTAC 100 from the body.

It may also be highly desirable to eliminate step 8, and also in step 1flush the internal volume/dead with the ablative fluid outside the body,instead of saline. This would be done with the guide tubes 115 andneedles 119 fully deployed. It may also be desirable if this techniqueis used to rinse the distal portion of the PTAC 100 in saline prior toadvancement of the catheter into the body in order to remove any of theablative fluid from the surface of the PTAC 100 that might have beenretained on the surfaces of the catheter during the flushing with theablative fluid.

While the buttons 332 and 342, as described above, release the motion ofcontrol cylinders when depressed and lock when released, it is alsoenvisioned that they could also be interlocked as follows:

-   -   1. The first interlock allows the injection needle control        cylinder 345 to be unlocked only when the guide tube control        cylinder 333 is in its most distal position where the outer tube        102 is pulled back and the guide tubes 115 are fully deployed.    -   2. The second interlock allows the guide tube control cylinder        333 to be unlocked only when the injection needle control        cylinder 345 is in its most distal position where the needles        119 are retracted within the guide tubes 115.

The combination of the buttons 332 and 342 with the control mechanismsdescribed above should make the use of the PTAC 100 reasonably simpleand straight forward. The operator basically presses button 332 andpushes the guide tube cylinder 333 forward causing the guide tubes 115to expand outward, then presses button 342 and advances the needles 119forward to penetrate the wall of the renal artery. Injections areperformed then the reverse procedure is done with button 342 depressedand the needles 119 retracted, then button 332 is depressed and theguide tube cylinder 333 is retracted in the proximal directionretracting the guide tubes 115 within the body of the PTAC 100.

While a push button activated handle where sections are pushed andpulled in the longitudinal direction to cause guide tube and needledeployment is shown in FIG. 11, it is envisioned that other techniquessuch as rotational mechanisms for locking or longitudinal motion canalso be used. The Fischell et at U.S. patent application Ser. No.13/643,070 filed Oct. 23, 2012, which is hereby incorporated byreference in its entirety, shows such a rotational locking mechanism inFIG. 33.

It is also envisioned that although flushing and filling the injectionlumens with normal saline as described in step 8 of the method above hasthe advantage of not allowing any of the toxic ablative fluid toaccidentally be introduced into the renal artery during the procedure,another technique is possible with a low dead space PTAC 100.Specifically if the dead space is small, and the ablative fluid isethanol, hypertonic or hypotonic saline, then the ablative fluid can beused to fill the dead space out of the body. Because of mixing withlarge amounts of blood going to the kidney, direct injection of even 0.5ml of ethanol, hypertonic or hypotonic saline will not harm the kidney.This concept then eliminates the flush step after injection of theablative fluid reducing the injection steps in the procedure from 2 perartery to one per artery. For example, if the dead space is 0.1 ml andthe desired injection volume of ethanol is 0.2 ml then 0.1 ml of ethanolcould be used to fill the dead space outside of the body. Then thecatheter and needles would be deployed in the first renal artery. Then0.2 ml additional ethanol would be injected which will deliver 0.2 mlinto the peri-vascular space leaving 0.1 ml in the dead space. Theneedles 119 and guide tubes 115 are refracted, the PTAC 100 is deployedin the other renal artery and another 0.2 ml of ethanol would beinjected. The needles 119 and guide tubes 115 are retracted and the PTAC100 is removed from the body. In this abbreviated procedure, very little(<0.05 ml) ethanol should leak out into the renal artery and 10 timesthat amount will still not harm the kidney. Another advantage of thisreduced step process is that only ablative fluid is delivered to theperi-vascular space which reduces the “dilution” of the ablative fluidby the volume of saline in the dead space that would be delivered firstin the procedure above before the ablative fluid can be delivered.

It should also be noted that in one variation of the procedure havingthe cap 356 locked onto to the fitting for the injection port 354 priorto placing the PTAC 100 into the patient's body will certainly preventany ablative solution from entering the renal artery during insertion ofthe PTAC 100 into the renal artery. Additionally, replacing that sealingcap 356 onto the fitting for the injection port 354 as the PTAC 100 ismoved from one renal artery to the opposite renal artery will alsoprevent any ablative solution from entering the second renal artery. Thecap 356 would also be locked onto the fitting for the injection port 354as the PTAC 100 is removed from the patient's body. During the renaldenervation procedure, the cap 356 would be removed only to injectablative solution into the peri-vascular space of the treated vessel.

A stopcock attached to the port 354 could also be used such that whenclosed, it would prevent leakage of ablative fluid out of the needledistal openings 117 of FIGS. 2 through 10. In reality of course, ifthere were no cap 356 attached as the PTAC 100 is moved within thearterial system of the body, the blood pressure within the arterialsystem would if anything force any fluid within the injection lumens ofthe PTAC 100 back out of port 354.

It is also envisioned that one could have any combination of use ornon-use of flushing steps. For example, the PTAC 100 dead space could beprefilled with the ablative fluid, and then saline solution could beused to flush the ablative fluid into the peri-vascular space followingdeployment of the needles 119 and guide tubes 115. After the ablativefluid has been injected into the peri-vascular space, the needles 119and guide tubes 115 could be retracted out of the peri-vascular spaceand the dead space could be refilled with ablative fluid flushing thesaline out of the dead space. The other renal artery could then betreated.

The PTAC 100 can be packaged with the guide tubes 115 fully extended andthe injector tubes 116 fully retracted. The reason for this is that thepreferred embodiment of the guide tubes are made from plastic such aspolyimide formed into a curve shape. Such a plastic material may loseits shape if it were packaged retracted back into the tubular shaft 120which would straighten it. It is also possible to ship the device withthe needles 119 at the distal end of the injector tubes 116 fullyexpanded as well to ensure maximum shape retention of the guide tubes115 and the injector tubes 116. In this case, the device would beshipped in a protective housing to ensure handlers do not receive needlesticks.

It should also be understood that the handle 300 in FIG. 11 has a distalportion that has a tapered cone structure 338 that is attached to ahypotube 82, which hypotube 82 extend for most of the length of the PTAC100. As shown in FIG. 18, the hypotube 82 is connected to a connectingtube 92 that is joined at its distal end to the outer tube 102 of thePTAC 100. A hypotube is typically made from the same type of metal as ahypodermic needle, e.g., typically a stainless steel.

FIG. 12 is a longitudinal cross-section of alternative embodiment of thePTAC 200 with self-expanding guide tubes 215 supported by anIntraluminal Centering Mechanism (ICM) 250 that assists in bothuniformity of expansion of the self-expanding guide tubes 215 as well asproviding addition support for the guide tubes 215. The central portion204 of the ICM 250 will provide a larger surface to open against theinterior wall of the target vessel to prevent the distal ends 229 of theguide tubes 215 from backing away from the interior wall of the targetvessel or moving laterally as the injector tubes 216 with distalinjection needles 219 are advanced outwardly through the vessel wall. Aswith the PTAC 100 of FIGS. 2 through 11, the guide tubes 215 are theneedle guiding elements that expand outwardly to provide support/backupfor the injection needles 219 at the distal end of the injector tubes216 as they are advanced through to penetrate the interior wall of thetarget vessel. This support or backup is an important feature of thisalternative embodiment of the PTAC 200 as shown in FIG. 12 compared withthe prior art PTAC 50 embodiment shown in FIG. 1. The PTAC 200 shown inFIG. 12 includes an obturator 220 having proximal section 223, distaltapered section 226 and radiopaque marker band 224. Distal to thetapered section 226 is a fixed guide wire 210 with core wire 211 andouter layer 228. A radiopaque wire 218 inside the lumen of each injectortube 216 provides enhanced radiopacity for the injector tubes 216 sothat their deployment can be visualized under fluoroscopy.

The PTAC 200 of FIG. 12 has four guide tubes 215 with four concentricinjector tubes 216. Ideally 3-5 needles should be used for renaldenervation. With ethanol as the ablative fluid for neural ablation,three needles may be sufficient because of the hydrophilic nature ofethanol which can readily spreads within human tissue.

The core wire 211 provides connectivity with the central section of thePTAC 200 and extends distally to form the core of the fixed guide wire210. Fixed wire devices and the formation of guide wires are well knownin the art of medical devices.

The ICM 250 includes a distal ring 202, support struts 208, centralportion 204 with radiopaque marker 206. The ICM 250 provides additionalradial and circumferential/lateral support for the guide tubes 215 bothduring expansion and during advancement of the injector tubes 216through the guide tubes 215. The outside of the central portion 204 alsoprovides a small but flat or slightly curved surface to engage or touchthe interior wall of the target vessel that can reduce the trauma to thevessel wall as compared with having the ends of the guide tubes 215touch the wall. As can be seen in FIG. 12, the surfaces 204 would touchthe wall of the vessel before the ends of the guide tubes 215 wouldtouch that wall. This design provides a broader surface in contact withthe vessel wall and that would eliminate any tendency for the distal end229 of the guide tubes 215 to damage the wall of the target vessel.

It is envisioned that there are several techniques for creating thestructure of guide tubes 215 attached to a distal ICM 250 as shown inFIGS. 12 and 13. One technique is to take a nitinol tube which will beformed into the shape seen in FIG. 12. Once heat set in this shape, amachining process would remove material to expose the distal ends 229 ofthe guide tubes 215. A second machining process would remove half of thecylinder say from 90 to 270 degrees of a portion of the ICM 250 of thePTAC 200. A radiopaque plug 206 would then be attached within thehorizontal section 204 and the distal end of the ICM 250 would beattached to the ring 202.

An alternative technique would have the guide tubes 215 made of plasticand a nitinol flat wire having three sections including a proximalsection attached to the plastic tube a central portion with a flathorizontal shape and a distal curved ICM portion.

A sheath 212 with radiopaque marker band 213 is shown in FIG. 12 in itsproximal or open position having been retracted to allow theself-expanding guide tubes 215 to expand outward. The radiopaque markers206 allow fluoroscopic visualization to confirm the appropriateexpansion of the guide tubes 215 against and/or in close proximity tothe interior wall of the target vessel. The injector tubes 216 withdistal injection needles 219 and distal opening 217 are then advancedthrough the guide tubes 215 to penetrate the interior wall of the targetvessel. Ablative fluid is then injected through the needle distalopenings 217 into the peri-vascular space. The injector tubes 216 arethen withdrawn back into the guide tubes 215 and the sheath 212 isadvanced in the distal direction to collapse the guide tubes 215 and theICM 250. When the radiopaque marker band 213 near the distal end of thesheath 212 is adjacent to the radiopaque marker 224 on the obturator220, the operator can confirm that the PTAC 200 is in its closedposition and retract it back into the guiding catheter.

FIG. 13 is a longitudinal cross-section enlargement of section S13 ofFIG. 12 showing the structure of the fully deployed PTAC 200. Theinjector tubes 216 with distal injection needles 219, needle distalopening 217 and radiopaque wire 218 are shown coaxially advanced out ofthe distal end 229 of the guide tube 215 with the ICM 250 attached. TheICM 250 has a central portion 204 with radiopaque marker 206. Thecentral portion 204 has a proximal end that is fixedly attached theguide tube 215 on its distal end. The central portion 204 is shown inFIG. 13 formed integral with the support strut 208 connecting at thedistal end of the central portion 204.

The guide tubes 215, central structure 204 and support struts 208 areformed from a shape memory alloy or springy metal such as nitinol.Specifically, in the embodiment shown in FIGS. 12 and 13, a single tubeof nitinol is machined and then bent and heat set to form theconfiguration shown in FIGS. 12 and 13. The guide tubes 215 arecylindrical as is the central section 204 which has a radiopaque marker206 attached to it. The support struts 208 have a portion of thecylinder removed.

It is also envisioned that the guide tubes 215 could be plastic such asshown in FIGS. 1-10 with a round or flat nitinol wire attached to theguide tube 215 to enhance the self-expansion characteristics of theplastic and extend distally to form the ICM support struts. It is alsoenvisioned that different variations in the structure of the guide tubes215 can be used to make the guide tubes more flexible. For example, ahelical laser cut out along the length of the guide tube 215.

FIG. 14 is an enlargement of the longitudinal cross-section of sectionS14 of the PTAC 200 of FIG. 12. FIG. 14 shows the sheath 212 with distalradiopaque marker band 213. Also shown are the guide tubes 215, theinjector tubes 216, the radiopaque wire 218 and the core wire 211. Thecentral and proximal sections of the PTAC 200 are shown in the priordisclosures of U.S. patent application Ser. Nos. 13/294,439 and13/342,521. This includes the mechanisms near the proximal end of thePTAC 200 that allow the operator to retract the sheath 212 allowing theguide tubes 215 to expand outward against the interior wall of thetarget vessel. This also includes the mechanism that controls theadvancement of the injector tubes 216 with distal injection needles 219through the guide tubes 215 and into the wall of the target vessel.

Fischell et al. in U.S. patent application Ser. No. 13/643,070 showsseveral handle/proximal section configurations specifically designed torelease self-expanding guide tubes and advance injection needles into ordeep to (outside of) the adventitia of a target vessel. Such designswould work well in conjunction with the PTAC 200 of FIGS. 12 through 14.

While the PTAC 200 of FIGS. 12 through 14 show a self-expanding guidetube structure, it is envisioned that an ICM could be added to themanually expanded PTAC 100 of FIGS. 2-10 to further enhance the supportand backup of the guide tubes against the interior wall of the targetvessel.

An important inventive feature of the PTAC 200 of the presentapplication is the use of radial and lateral/circumferential supportstructures for the needle guiding elements/guide tubes 115 and guidetubes 215 of FIG. 4 and FIG. 12. These include the tubular shafts 120with openings 131 and central buttress 121 to provide both radial andlateral support for the guide tubes 115 of FIG. 4 and the ICM 250 ofFIG. 12 to provide radial and lateral support for the guide tubes 216.

FIG. 15 is a longitudinal cross-section of PTAC 300 which is anotherembodiment of the present application. This design has the guide tubes316 and injector tubes 318 combined into a single injector tube assembly315 with radiopaque marker 322, distal end 329 and distal injectionneedle 319 having distal opening 317 and a gold plating on the outsideof the injector tubes 318 to enhance visibility of the needles 319 underfluoroscopy. The PTAC 300 has a distal tapered nose 306, outer tube 302with openings 331 through which the injector tube assembly 315 isadvanced.

The PTAC 300 also has an inner tube 305 with injection lumen 333 whichis in fluid communication with the lumens of the injector/guide tubeassemblies 315 which is in fluid communication with the lumen of theinjection needle 319. The inner tube 305 is attached to theinjector/guide tube assembly 315 through the manifold 325. The centralbuttress 321, similar to that of the central buttress 121 of FIGS. 3 and4, provides the ramp 344 that deflects the injector tube assembly 315outward and provides radial support for the penetration of the interiorwall of the target vessel by the injection needles 319.

The distal nose 345 of the central buttress 321 provides the attachmentfor the nose 306. The outer tube 302, distal nose 306 or centralbuttress 321 may also include radiopaque markers or be made from aplastic with a radiopaque filler such as tungsten filled polyurethane.The central buttress 321 must extend a sufficient distance in theproximal direction so that the needle distal opening 317 can becompletely withdrawn within the body of the PTAC 300 to avoidneedlestick injuries to users of the PTAC 300.

The distal nose 306 would preferably be made from a relatively lowdurometer or soft plastic. The needles 319 can be made from any metalthat will hold its shape although cobalt chromium alloys such as L605 ora shape memory metal alloy such as nitinol are preferred.

It is also envisioned that the PTAC 300 could have a distal fixed guidewire like the PTAC 100 of FIG. 3 or be configured to be delivered over aguide wire in either an over-the-wire or rapid exchange configuration.Similarly, the PTAC 100 of FIGS. 2-11 or the PTAC 200 of FIGS. 12through 14 could use a soft nose similar to the nose 306 of FIG. 15instead of a fixed guide wire 211 as shown for other embodimentsdisclosed in the present application.

The PTAC 300 can be substantially similar to the PTAC 100, and can beused in substantially similar manner as described herein. The PTAC 300has the advantage of one less step in delivery of the needles ascompared to the PTAC 100 of FIGS. 2-11. After positioning the distal endof the PTAC 300 at the desired site, the operator can advance the innertube 305 with respect to the outer tube 302 using a mechanism at theproximal end of the PTAC 300. This will push the injector tubeassemblies 315 forward and outward as deflected by the ramps 344 of thecentral buttress 321 and out of the openings 331 in the outer tube 302.The needles 319 will penetrate the interior wall of the target vessellimited in penetration by the distal ends of the injector/guide tubeassemblies 315. The combination of the radiopaque marker bands 322 onthe assemblies 315 and the gold plating on the needles 319 allows theuser to visualize the deployment of the PTAC 300 for delivering anablative fluid into the peri-vascular space.

In this embodiment of the PTAC 300, the injector/guide tube assemblies315 are the needle guiding elements that expand outward to providesupport/backup for the injection needles 319 as they are advancedthrough the wall of the target vessel.

FIG. 16 is a longitudinal cross-section of the distal portion of stillanother embodiment of the presently disclosed PTAC 400, which uses aninflatable balloon 450 to expand the four guide tubes 415 outward toengage the interior wall of the target vessel. Three to eight guidetubes are envisioned for this design with three being preferred fordelivery of ethanol for renal denervation. The balloon 450 can be acylindrical balloon. The balloon 450 can be designed to avoidobstructing blood flow within the target vessel, even when expanded, asdescribed herein. It can also be a non-compliant balloon to ensureluminal space between the outside of the balloon and the inside wall ofthe target vessel for blood to flow.

The PTAC 400 has a distally attached fixed guide wire 420 with outerlayer 425, core wire 411 and distal tip 428. FIG. 16 shows the PTAC 400in its fully open position with guide tubes 415 with radiopaque markers422. Coaxially within the guide tubes 415 are injector tubes 416 withsharpened distal injection needles 419 with distal openings 417 deployedoutward beyond the distal ends 429 of the guide tubes 415. A radiopaquewire 418 lies within the lumen of the injector tube 416 to reduce thedead space and provide enhanced visibility.

The distal portion of the PTAC 400 has the tapered section 426,radiopaque marker band 424 and proximal portion 423. This tapered unit,including elements 423, 424 and 426, is called an obturator 430. Theobturator 430 is attached to the fixed guide wire 420 with tip 428,outer layer 425 and core wire 411. Other important features of thisalternative embodiment are the radiopaque marker band 413 on the sheath402 that in combination with the radiopaque marker band 424 on theobturator 430, provides indication of the position of the distal end ofthe sheath 402 relative to the obturator 430 so that the operatorreadily knows whether the PTAC 400 is in its closed position with thesheath 402 in its fully distal position and the guide tubes 415 andinjector tubes 416 are thereby fully enclosed. The obturator can belongitudinally movable with respect to PTAC 400.

The preformed radius of curvature of the injector tubes 416 should besimilar to that of the guide tubes 415 so that the guide tubes 415 willmaintain their position against the interior wall of the target vesselas the injector tubes 416 with distal injection needles 419 are advancedto penetrate the interior wall of the target vessel. Specifically, theradius of curvature of the central axis of the distal portion of theinjector tube 416 should be approximately the same as the radius ofcurvature of the central axis of the guide tube 415. The radii ofcurvature of the central axes of the guide tubes 415 and the injectortubes 416 can be within 1 mm of each other, or within 0.2 mm of eachother. Although a curved shape with a single radius of curvature isshown in FIG. 16, curved shapes of the guide tubes 415 and injectortubes 416 could have two or more portions each with a different radiusof curvature. Even if two or more different radii of curvature are usedfor these components, it can be advantageous that when fully deployed,the curved shape of the injector tube 416 is such that its longitudinalaxis is coaxial to the longitudinal axis of the lumen of the curvedportion or portions of the guide tube 415. In other words, the advancedinjector tube 416 can in some embodiments fit perfectly within theadvanced guide tube 415. It is also envisioned that if the radii ofcurvature are significantly different then the radius of curvature ofthe injector tube 416 should be less than the radius of curvature of theguide tube 415 so that when the injector tube 416 is advanced it willnot push the guide tubes 415 away from the interior wall of the vessel.Another way to characterize the two radii of curvature is that theyshould be, in some cases, within about 20% of each other and in someembodiments within 5%.

As with the PTAC 100 of FIGS. 2 through 11, the guide tubes 415 are theneedle guiding elements that expand outwardly to provide support/backupfor the injection needles 419 at the distal end of the injector tubes416 as they are advanced through the needle guiding elements topenetrate the wall of the target vessel.

FIG. 16 shows an inflatable balloon 450 attached at its proximal end tothe tube 405 and at its distal end to the obturator 430. Side holes 452in the inner tube 405 provide fluid communication between the inflationlumen 433 of the inner tube 405 and the interior space 454 of theinflatable balloon 450. The inflatable balloon 450 can include adeflection surface, the deflection surface deflecting the distallymoving guide tubes outward toward the interior wall of the targetvessel. This design provides significant enhancement in radial stabilityof the guide tubes 415 as compared to the design of the INAS 50 as shownin FIG. 1. This is because the balloon 450 provides significant radialsupport for the guide tubes 415.

The PTAC 400 guide tubes 415 may be advanced and retracted similar toother embodiments. For example, the guide tubes can be slid along theoutside of the inflatable balloon 450, as if the inflatable balloon 450were a central buttress 121. The expanded surface of the inflatableballoon 450 provides a deflection surface of the distally moving guidetubes 415, which deflects the guide tubes outward toward the interiorwall of the vessel. In this embodiment, the PTAC 400 functions similarlyto PTAC 100.

In other embodiments, the outside of the balloon 450 is optionallyfixedly attached to each guide tube 415. In this configuration, theballoon 450, being attached to the guide tubes 415, will enhance thelateral stability of the guide tubes 415 for uniform expansion andimproved centering of the distal portion of the PTAC 400. It isenvisioned that there are several techniques for creating the structureof guide tubes 415 attached to the balloon 450. Upon expansion, theinflatable balloon 450 deflects the guide tubes outward toward theinterior wall of the vessel.

In some embodiments, the expanded balloon 450 can be designed to besmaller than the lumen of the target vessel. In some embodiments, theguide tubes 415 extend beyond the expanded balloon 450. In FIG. 16, theguide tubes 415 with radiopaque markers 422 extend beyond the surface ofthe balloon 450. When expanded, the balloon 450 would not obstruct bloodflow. The blood would be able to flow around the balloon, for examplenear the radiopaque markers 422 as shown in FIG. 16. The balloon 450 canbe a non-compliant balloon to ensure there is space between the outsideof the balloon and the inside wall of the target vessel for blood toflow.

In some embodiments, the guide tubes 415 may be attached to the innertube 405. Then, only the injector tubes 416 would be capable oflongitudinal movement within the PTAC 400.

Similar to prior embodiments the PTAC 400 can be configured to beadvanced over a separate guide wire or have no guide wire at all. Alsothe guide tubes 415 and injector tube 416 can be combined similar to thedesign of the PTAC 300 of FIG. 15.

For the configuration shown in FIG. 16, a sheath 402 with distalradiopaque marker band 413 has been pulled back to allow the guide tubes415 to expand outwardly. The radiopaque wire 418 and the radiopaquemarker bands 422, 424 and 413 may be made from any high density metalsuch as gold, platinum or tantalum or an alloy of such metals.

The balloon 450 may be compliant, semi-compliant or non-compliant,however an elastic compliant balloon can be preferred as it allowsdiameter of the expanded guide tubes 415 to be easily set by usingdifferent inflation pressures for the balloon 450. Attaching the guidetubes 415 to the outside of the balloon simplifies construction ascompared to attempting to place guide tubes 415 within the balloon. Thisdesign also allows the distal end 429 of the guide tubes 415 to be thepoints of engagement with the interior wall of the target vessel so thatthe entire balloon 450 does not touch the wall. Having the balloon 450touch the wall can remove some endothelial cells and produce neointimalhyperplasia which is undesirable. The balloon could typically beinflated to a pressure between 10 and 100 psi by injection of normalsaline through the inflation lumen 433.

While FIG. 16 shows an inflatable balloon 450 used to provide radial andlateral support for the guide tubes 415, it is envisioned that anymechanical structure that can be expanded under the guide tubes 415could be used. Such a structure may or may not actually be attached tothe guide tubes. For example a structure similar to that of many carjacks that when the ends come together opens up could be used. A screwthread or just a wire or tube that pulls the ends together would besufficient to form a structure that would support the guide tubes 415

It is also envisioned that an inflatable balloon such as the balloon 450of FIG. 16 could be added to the PTAC 200 with intravascular centeringmechanism (ICM) 250 of FIG. 12. This would be applicable whether theguide tubes 215 with ICM 250 are self-expanding or manually expandable.

FIG. 17 is a schematic view of the central buttress 121 of the PTAC 100of FIGS. 3 and 4. The distal tip 145 with neck 146 provides attachmentto the proximal portion of the distal tip 106 of the PTAC 100 as shownin FIGS. 3 and 4. The curved ramps 144 provide radial and lateralsupport for the guide tubes 115 as they are advanced forward and slidealong and outward as directed by the curved ramps 144. The distalfingers 142 have beveled inside surfaces 148 that also provide lateralsupport for the guide tubes 115 as they are advanced. The curvedstructures 142 (as can be seen in FIG. 4) are attached inside of theouter tube extension 104.

FIG. 18 illustrates longitudinal cross-sections of three centralportions of the PTAC 100 of FIGS. 2 through 11. At the proximal end ofthe central portion of the PTAC 100 are three concentric metalhypotubes, an outer hypotube 82, middle hypotube 83 and inner hypotube85. These are typically made from thin walled metallic tubing such asstainless steel, L605, cobalt chromium or nitinol. The outer hypotube 82of the PTAC 100 attaches at its distal end to a proximal plastic outertube 92 typically made from a relatively high durometer plastic, forexample polyimide. As seen in the central cross-section of FIG. 18, theproximal plastic tube 92 attaches at its distal end to the proximal endof the outer tube 102 also shown in FIGS. 2 through 11. The outer tube102 is typically made from a lower durometer/more flexible plastic thanthe proximal plastic tube 92.

As shown in the proximal section of FIG. 18, the middle hypotube 83 isattached at its distal end to the middle tube 103. As shown in thecentral section of FIG. 18, the inner hypotube 85 with central injectionlumen 93 is attached at its distal end to the proximal end of the innertube 105 having an injection lumen 133.

Also shown in distal section of FIG. 18 is the manifold 125 thatconnects the inner tube 105 to the injector tubes 116 of FIGS. 3 and 4and the radiopaque wires 118 that run the length of the injector tubes116 to provide visibility under fluoroscopy. The manifold 125 liescoaxially within the inner tube 105 in a portion of the inner tube 105that is proximal to the distal end of the inner tube 105. The proximalend of the inner tube 105 is also coaxially positioned within the outertube 102 which is proximal to the outer tube extension 104 of FIGS.2-10.

FIG. 19 is a schematic view of the distal end of the fully expanded PTAC100 of FIGS. 2 through 10 showing the orientation of the sharpenedinjection needles 119 with respect to the distal end of the PTAC 100.FIG. 19 is the view looking down the longitudinal axis of the PTAC 100from its distal end. The tip of the guide wire 109 and tapered distalsection 106 are clearly seen as are the three expanded guide tubes 115with radiopaque markers 122. The expanded injector tubes 116 with distalinjection needles 119 are shown with the cut portion of the needles 119being cut so that the open face of the needle 119 will deliver theablative fluid in a direction that is perpendicular to the longitudinalaxis of the PTAC 100 and the face of the bevel cut of the needle 119faces laterally with respect to the axis of the needle 119.

This configuration is advantageous as it reduces the probability thatthe point of the needle 119 will get caught on the inside of the guidetube 115 as the needle 119 is advanced.

FIG. 20 is a schematic view of an enlargement of section S20 of FIG. 19showing a preferred shape of the sharpened injection needles 119. FIG.20 shows a direction of ablative fluid flow from the needle distalopening 117 that is perpendicular to the longitudinal axis of the PTAC100. Also shown is the additional cut 91 in the needle tip 81 whichprovides a sliding surface. The direction of the main cut of the needle119 as well as the additional cut 91 combine to reduce the chance ofhaving the needle tip 81 accidently get caught on the inside of theguide tube 115 as the needle 119 is advanced through the guide tube 115.

FIG. 21A is a schematic view of an alternative embodiment which is thePTAC 500. The PTAC 500 uses the proximal portion of the obturator 520 asthe support structure for the guide tubes 515. The obturator 520 hasproximal section 523, radiopaque marker band 524 and distal taperedsection 506. The proximal section 523 has slots 525 into which the guidetubes 515 will nest or fit. The outer tube 502 forms the outside of thePTAC 500 and acts as a sheath that can be advanced over the proximalportion 523 of the obturator 520 to form a closed structure. The innertube 505 is a tube within the structure of the outer tube 502 whichprovides the impetus for motion of the injection needles 519 (notshown). The wire 503 is the structure which provides the impetus formotion of the guide tubes 515. The core wire 511 is connected to theobturator 520 and a mechanism at the proximal end of the PTAC 500facilitates longitudinal motion of the obturator 520 with respect to theouter tube 502 and/or guide tubes 515. A fixed guide wire 509 is shownalthough the PTAC 500 could be configured to be delivered over a guidewire or with a distal end with no guide wire such as the PTAC 300 ofFIG. 15.

FIG. 21A shows the configuration of the PTAC 500, after the guide tubes515 are advanced, but before the needles 519 are advanced. The guidetubes 515 can be manually advanced as they are with the PTAC 100 ofFIGS. 2 through 11 or they can be self-expanding as in the prior artPTAC 50 of FIG. 1 when the outer tube 502 acts as a sheath and is pulledback to allow the guide tubes 515 to expand outwardly. The next stepfollowing the configuration of FIG. 21A, is for the obturator 520 to bemoved proximally (pulled back) by the proximal motion of the core wire511 actuated by the mechanism in the proximal section of the PTAC 500.This will cause the slots 525 to move proximally until they nest upagainst the expanded guide tubes 515 providing both radial and lateralsupport, similar to the central buttress 121 shown in FIG. 17. Once theobturator 520 is pulled back, the needles 519 are advanced into the wallof the target vessel in the configuration shown in FIG. 21B.

FIG. 21B shows the configuration of the PTAC 500 following advancementof the needles 519 at the distal ends of the injector tubes 516 into thewall of the target vessel. The obturator 520 provides radial support forthe guide tubes 515 to prevent them backing away from the interiorvessel wall as the needles 519 are advanced. The slots 525 also providelateral support to keep the guide tubes 515 and needles 519 positionedat 120 degrees with respect to each other for uniform injection of theablative fluid into or outside of the wall of the target vessel. As inprior embodiments, the guide tubes 515 are the needle guiding elements.In this embodiment the obturator 520 is a longitudinally movablemechanism that provides the radial and lateral support for the needleguiding elements which are the guide tubes 515.

While this specification has focused on use of the PTAC for use inablation of tissue, it is also clearly envisioned that the apparatus andmethods of FIGS. 1-21B inclusive can be applied to inject any fluid forany purpose including that of local drug delivery into a specifiedportion of a blood vessel or the volume of tissue just outside of ablood vessel, or into prostatic tissue via the prostatic urethra.

While the embodiments shown in FIGS. 1 through 21B show either three orfour injection needles, the presently disclosed structure which includesradial and/or lateral support mechanisms for needle guiding elementsthat guide injection needles as they penetrate the interior wall of atarget vessel can be applied to designs with one needle, two needles or5 or more needles. Even a single needle design would be of smallerdiameter and easier to use than other single needle systems such as theBullfrog system of Mercator.

Various other modifications, adaptations, and alternative designs are ofcourse possible in light of the above teachings. Therefore, it should beunderstood at this time that within the scope of the appended claims theinvention may be practiced otherwise than as specifically describedherein. It is contemplated that various combinations or subcombinationsof the specific features and aspects of the embodiments disclosed abovemay be made and still fall within one or more of the inventions.Further, the disclosure herein of any particular feature, aspect,method, property, characteristic, quality, attribute, element, or thelike in connection with an embodiment can be used in all otherembodiments set forth herein. Accordingly, it should be understood thatvarious features and aspects of the disclosed embodiments can becombined with or substituted for one another in order to form varyingmodes of the disclosed inventions. Thus, it is intended that the scopeof the present inventions herein disclosed should not be limited by theparticular disclosed embodiments described above. Moreover, while theinvention is susceptible to various modifications, and alternativeforms, specific examples thereof have been shown in the drawings and areherein described in detail. It should be understood, however, that theinvention is not to be limited to the particular forms or methodsdisclosed, but to the contrary, the invention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the various embodiments described and the appended claims.Any methods disclosed herein need not be performed in the order recited.The methods disclosed herein include certain actions taken by apractitioner; however, they can also include any third-party instructionof those actions, either expressly or by implication. For example,actions such as “expanding a balloon” include “instructing the expandingof a balloon.” The ranges disclosed herein also encompass any and alloverlap, sub-ranges, and combinations thereof. Language such as “up to,”“at least,” “greater than,” “less than,” “between,” and the likeincludes the number recited. Numbers preceded by a term such as“approximately”, “about”, and “substantially” as used herein include therecited numbers (e.g., about 10%=10%), and also represent an amountclose to the stated amount that still performs a desired function orachieves a desired result. For example, the terms “approximately”,“about”, and “substantially” may refer to an amount that is within lessthan 10% of, within less than 5% of, within less than 1% of, within lessthan 0.1% of, and within less than 0.01% of the stated amount.

What is claimed is:
 1. A method of treating hypertension, comprising:positioning a distal portion of a delivery catheter within a renalartery; advancing at least three guide tubes from the delivery catheteruntil a distal end of each of the at least three guide tubes touch aninside wall of the renal artery, wherein advancing at least three guidetubes further comprises advancing at least three guide tubes withoutinflating a balloon; advancing at least three injection needles throughthe at least three guide tubes and into a peri-vascular space outside ofan inside surface of the renal artery; and injecting an ablative fluidthrough the at least three injection needles to form at least threeablative fluid zones in the peri-vascular space; wherein the at leastthree ablative fluid zones intersect to form an ablation ring around acircumference of and outside of the inside surface of the renal artery.2. The method of treating hypertension as in claim 1, wherein injectingthe ablative fluid comprises injecting ethanol.
 3. The method oftreating hypertension as in claim 1, wherein injecting the ablativefluid comprises injecting from 0.1 ml to 3.0 ml of the ablative fluid.4. The method of treating hypertension as in claim 1, wherein injectingthe ablative fluid comprises injecting a volume of less than 0.5 ml ofthe ablative fluid.
 5. The method of treating hypertension as in claim1, wherein injecting the ablative fluid comprises injecting the ablativefluid at a distance of between 0.5 mm to 4 mm beyond an internal elasticlamina.
 6. The method of treating hypertension as in claim 1, whereininjecting the ablative fluid comprises injecting the ablative fluid at adistance of between 4 mm to 8 mm beyond an internal elastic lamina. 7.The method of treating hypertension as in claim 1, further comprisingpermitting perfusion in a vessel across the distal portion of thedelivery catheter, following advancing the at least three guide tubes.8. The method of treating hypertension as in claim 1, wherein advancingthe at least three guide tubes comprises advancing the at least threeguide tubes along a central buttress which supports the at least threeguide tubes.
 9. The method of treating hypertension as in claim 1,further comprising fluoroscopically visualizing the at least three guidetubes following advancing the at least three guide tubes.
 10. The methodof treating hypertension as in claim 1, wherein advancing at least threeguide tubes further comprises advancing at least three guide tubes fromat least three openings in the delivery catheter.
 11. The method oftreating hypertension as in claim 1, wherein the three ablative fluidzones extend from the distal ends of the at least three guide tubes. 12.The method of treating hypertension as in claim 1, wherein the at leastthree guide tubes include a shape memory metal.
 13. A method of treatinghypertension, comprising: positioning a distal portion of a deliverycatheter within a renal artery; advancing at least three guide tubesfrom the delivery catheter until a distal end of each of the at leastthree guide tubes touch an inside wall of the renal artery, wherein theat least three guide tubes form a curve upon removal of a restraint;advancing at least three injection needles through the at least threeguide tubes and into a peri-vascular space outside of an inside surfaceof the renal artery; and injecting an ablative fluid through the atleast three injection needles to form at least three ablative fluidzones in the peri-vascular space; wherein the at least three ablativefluid zones intersect to form an ablation ring around a circumference ofand outside of the inside surface of the renal artery.
 14. The method oftreating hypertension as in claim 13, wherein injecting the ablativefluid comprises injecting ethanol.
 15. The method of treatinghypertension as in claim 13, wherein injecting the ablative fluidcomprises injecting from 0.1 ml to 3.0 ml of the ablative fluid.
 16. Themethod of treating hypertension as in claim 13, wherein injecting theablative fluid comprises injecting a volume of less than 0.5 ml of theablative fluid.
 17. The method of treating hypertension as in claim 13,wherein injecting the ablative fluid comprises injecting the ablativefluid at a distance of between 0.5 mm to 4 mm beyond an internal elasticlamina.
 18. The method of treating hypertension as in claim 13, whereininjecting the ablative fluid comprises injecting the ablative fluid at adistance of between 4 mm to 8 mm beyond an internal elastic lamina. 19.The method of treating hypertension as in claim 13, further comprisingpermitting perfusion in a vessel across the distal portion of thedelivery catheter, following advancing the at least three guide tubes.20. The method of treating hypertension as in claim 13, whereinadvancing the at least three guide tubes comprises advancing the atleast three guide tubes along a central buttress which supports the atleast three guide tubes.
 21. The method of treating hypertension as inclaim 13, further comprising fluoroscopically visualizing the at leastthree guide tubes following advancing the at least three guide tubes.22. The method of treating hypertension as in claim 13, wherein the atleast three guide tubes include a shape memory metal.
 23. A method oftreating hypertension, comprising: positioning a distal portion of adelivery catheter within a renal artery; advancing at least three guidetubes from the delivery catheter until a distal end of each of the atleast three guide tubes touch an inside wall of the renal artery,wherein the at least three guide tubes are self-expanding; advancing atleast three injection needles through the at least three guide tubes andinto a peri-vascular space outside of an inside surface of the renalartery; and injecting an ablative fluid through the at least threeinjection needles to form at least three ablative fluid zones in theperi-vascular space; wherein the at least three ablative fluid zonesintersect to form an ablation ring around a circumference of and outsideof the inside surface of the renal artery.
 24. The method of treatinghypertension as in claim 23, wherein injecting the ablative fluidcomprises injecting ethanol.
 25. The method of treating hypertension asin claim 23, wherein injecting the ablative fluid comprises injectingfrom 0.1 ml to 3.0 ml of the ablative fluid.
 26. The method of treatinghypertension as in claim 23, wherein injecting the ablative fluidcomprises injecting a volume of less than 0.5 ml of the ablative fluid.27. The method of treating hypertension as in claim 23, whereininjecting the ablative fluid comprises injecting the ablative fluid at adistance of between 0.5 mm to 4 mm beyond an internal elastic lamina.28. The method of treating hypertension as in claim 23, whereininjecting the ablative fluid comprises injecting the ablative fluid at adistance of between 4 mm to 8 mm beyond an internal elastic lamina. 29.The method of treating hypertension as in claim 23, further comprisingpermitting perfusion in a vessel across the distal portion of thedelivery catheter, following advancing the at least three guide tubes.30. The method of treating hypertension as in claim 23, whereinadvancing the at least three guide tubes comprises advancing the atleast three guide tubes along a central buttress which supports the atleast three guide tubes.
 31. The method of treating hypertension as inclaim 23, further comprising fluoroscopically visualizing the at leastthree guide tubes following advancing the at least three guide tubes.32. The method of treating hypertension as in claim 23, wherein the atleast three guide tubes include a shape memory metal.